Posts Tagged Neurogenesis

[WEB SITE] Human brains make new nerve cells — and lots of them — well into old age.

Previous studies have suggested neurogenesis tapers off or stops altogether

nerve cells in hippocampi

NEURON NURSERY  Roughly the same number of new nerve cells (dots) exist in the hippocampus of people in their 20s (three hippocampi shown, top row) as in people in their 70s (bottom). Blue marks the dentate gyrus, where new nerve cells are born.

Your brain might make new nerve cells well into old age.

Healthy people in their 70s have just as many young nerve cells, or neurons, in a memory-related part of the brain as do teenagers and young adults, researchers report in the April 5 Cell Stem Cell. The discovery suggests that the hippocampus keeps generating new neurons throughout a person’s life.

The finding contradicts a study published in March, which suggested that neurogenesis in the hippocampus stops in childhood (SN Online: 3/8/18). But the new research fits with a larger pile of evidence showing that adult human brains can, to some extent, make new neurons. While those studies indicate that the process tapers off over time, the new study proposes almost no decline at all.

Understanding how healthy brains change over time is important for researchers untangling the ways that conditions like depression, stress and memory loss affect older brains.

When it comes to studying neurogenesis in humans, “the devil is in the details,” says Jonas Frisén, a neuroscientist at the Karolinska Institute in Stockholm who was not involved in the new research. Small differences in methodology — such as the way brains are preserved or how neurons are counted — can have a big impact on the results, which could explain the conflicting findings. The new paper “is the most rigorous study yet,” he says.

Researchers studied hippocampi from the autopsied brains of 17 men and 11 women ranging in age from 14 to 79. In contrast to past studies that have often relied on donations from patients without a detailed medical history, the researchers knew that none of the donors had a history of psychiatric illness or chronic illness. And none of the brains tested positive for drugs or alcohol, says Maura Boldrini, a psychiatrist at Columbia University. Boldrini and her colleagues also had access to whole hippocampi, rather than just a few slices, allowing the team to make more accurate estimates of the number of neurons, she says.

To look for signs of neurogenesis, the researchers hunted for specific proteins produced by neurons at particular stages of development. Proteins such as GFAP and SOX2, for example, are made in abundance by stem cells that eventually turn into neurons, while newborn neurons make more of proteins such as Ki-67. In all of the brains, the researchers found evidence of newborn neurons in the dentate gyrus, the part of the hippocampus where neurons are born.

Although the number of neural stem cells was a bit lower in people in their 70s compared with people in their 20s, the older brains still had thousands of these cells. The number of young neurons in intermediate to advanced stages of development was the same across people of all ages.

Still, the healthy older brains did show some signs of decline. Researchers found less evidence for the formation of new blood vessels and fewer protein markers that signal neuroplasticity, or the brain’s ability to make new connections between neurons. But it’s too soon to say what these findings mean for brain function, Boldrini says. Studies on autopsied brains can look at structure but not activity.

Not all neuroscientists are convinced by the findings. “We don’t think that what they are identifying as young neurons actually are,” says Arturo Alvarez-Buylla of the University of California, San Francisco, who coauthored the recent paper that found no signs of neurogenesis in adult brains. In his study, some of the cells his team initially flagged as young neurons turned out to be mature cells upon further investigation.

But others say the new findings are sound. “They use very sophisticated methodology,” Frisén says, and control for factors that Alvarez-Buylla’s study didn’t, such as the type of preservative used on the brains.

via Human brains make new nerve cells — and lots of them — well into old age | Science News


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[WEB SITE] Newborn Neurons in the Adult Brain: Real Deal, or Glial Imposters? – Full Text Article

Deep in the hippocampus, are new neurons born throughout life? Just when scientists were about to reach some consensus that the answer was yes, two recent studies disagree. In the April 5 Cell Stem Cell, Maura Boldrini and colleagues at Columbia University, New York, report that adult neurogenesis not only exists, but remains steady into old age. The researchers counted newborn neurons in samples from people aged 14–79 years, and came up with similar numbers. In the March 7 Nature, researchers led by Arturo Alvarez-Buylla at the University of California, San Francisco, reported that while neural progenitors abounded in postmortem hippocampi from prenatal or early childhood brains, they fell off the map by age 7. What gives? In older people, some of the cells that expressed markers of budding neurons turned out to be glia, the authors claim.

  • Neural progenitor cells proliferate in human hippocampus throughout adulthood, says a new study.
  • It blames waning angiogenesis, not faulty neurogenesis, for lost neuroplasticity in old age.
  • In contrast, another paper claims brain neurogenesis fizzles during childhood.
  • It claims some cells bearing neural progenitor markers are actually glia.

Who is right? Researchers who spoke with Alzforum stood squarely behind Boldrini because she used stereology, a gold standard quantitation method, to estimate numbers of neural progenitors throughout the entire dentate gyrus of postmortem brain. Alvarez-Buylla’s team estimated cell numbers using only three to five slices from each postmortem sample. “It would be very difficult to rule out neurogenesis by this method,” said Orly Lazarov of the University of Illinois in Chicago, who pointed out that because the study relied on small numbers of individuals per age group, the data could be misleading.

Others, including Jonas Frisén of the Karolinska Institute in Stockholm, pointed to a long list of previous papers supporting the existence of neurogenesis in the adult human brain. “An analogy is that 10 people go into the woods to search for blueberries,” he wrote, “Nine come back with blueberries and one does not. Are there blueberries in that forest?”

Tracking Neurogenesis.
Scientists used a combination of cell-surface markers to count neural progenitors along the development spectrum in the dentate gyrus. While neurogenesis held steady, angiogenesis and neuroplasticity declined with age. [Courtesy of Boldrini et al., Cell Stem Cell, 2018.]

Still, others acknowledged that some of those “blueberries” might have been glia. “To me, it boils down to a single question: are these proliferating cells truly neural progenitors, or not?” asked Costantino Iadecola of Weill Cornell Medical College in New York.

Numerous studies in rodents support the idea that neural progenitors in the mammalian brain continue to trickle out fresh neurons into adulthood, though factors such as aging and disease dampen the flow (Altman and Das, 1965Sep 2001 newsFeb 2002 newsKempermann et al., 2003Mar 2010 news). Tracking neurogenesis in humans has been trickier, but a seminal study two decades ago set the stage: Five terminal cancer patients received an injection of bromodeoxyuridine (BrdU), a dye that incorporates into DNA during cell division. Postmortem analyses revealed evidence of dividing neurons in the dentate gyri of all of the patients (Eriksson et al., 1998). Since then, carbon-14 tracing and immunohistochemistry studies have supported the idea that new neurons arise in the adult human brain (Knoth et al., 2010Jun 2013 newsFeb 2014 news).

Boldrini and colleagues set out to determine if age affects adult neurogenesis. They acquired hippocampal samples from 11 women and 17 men, aged 14–79, who were cognitively normal, had suffered no brain trauma, had had no microvascular pathology in the brain, and had clean toxicology reports at the time of death. The researchers collected 50-micron thick sections every 2 mm along the entirety of the hippocampus, and used both immunofluorescence and immunocytochemistry to label various cell-surface markers associated with five different stages of neural development (see image below). Finally, they estimated cell numbers throughout the dentate gyrus using stereology, whereby a computer algorithm calculates total cell numbers in a region by combining data from multiple sections. They reported the number of neural progenitors in the anterior, mid-, and posterior dentate gyrus.

The earliest neural progenitors known, called quiescent radial-like type I neural progenitors (QNPs), express GFAP, a marker shared with astrocytes; nestin, an intermediate filament protein that marks neural stem cells; and the transcription factor Sox2, which is required for the maintenance of multipotent stem cells. The researchers found that numbers of these cells decreased with age in the anterior-mid dentate gyrus. This is in keeping with the prevailing view that people are born with a finite number of these QNPs, Boldrini said.

QNPs give rise to type II intermediate neural progenitors. INPs are proliferating cells that express Ki67, a marker of actively dividing cells. Neuroblasts, or type III INPs, also proliferate, but lose expression of GFAP and Sox2. Based on expression of Ki67, nestin, and Sox2, the researchers determined that numbers of type II and III INPs remained steady, on the order of thousands of cells, in all three regions of the dentate gyrus throughout life. These neural progenitors were found in the subgranular zone (SGZ), which is proposed to be the predominant neurogenic niche in the region, as well as the granule cell layer (GCL, see image below). The findings pointed to a stable supply of neural progenitors in the dentate gyrus throughout adult life.

The researchers next asked whether those progenitors would fulfill their destiny and give rise to immature neurons and, ultimately, bona fide granule neurons. On the way to becoming fully fledged neurons, type III INPs start to express doublecortin (DCX), a microtubule-associated protein involved in neural migration. They also produce polysialylated neural cell adhesion molecule (PSA-NCAM), a glycoprotein they need for plasticity. Together, DCX and PSA-NCAM mark young neurons, which continue to express both proteins until they differentiate into mature neurons, whereupon they suppress DCX. The researchers found that the tissue donors had similar numbers of cells co-expressing DCX and PSA-NCAM, regardless of their age, suggesting neurogenesis continued unabated throughout life. Numbers of NeuN+ mature neurons also held steady, indicating that neuronal loss in the dentate gyrus is not a characteristic of healthy aging, either.

The researchers calculated that each dentate gyrus had between 10,000 and 15,000 young neurons (i.e., type III INPs and immature neurons). While the functional significance of these cell numbers is unclear, Boldrini speculated that this ongoing level of neurogenesis influences neural circuitry and cognition. For this reason, boosting neurogenesis could be a therapeutic strategy for neurodegenerative disease, she said.

A New Neuron?
An immature neuron (red arrow) co-expressing PSA-NCAM and DCX lingers between the subgranular zone (SGZ) and the granule cell layer (GCL) in the dentate gyrus. Two other PSA-NCAM+ cells do not express DCX (yellow arrows).[Courtesy of Boldrini et al., Cell Stem Cell, 2018.]

However, while older adults appear to generate as many new neurons as younger people, those new cells may be less plastic, judging by a decline in PSA-NCAM+/DCX– cells in the anterior dentate gyrus. Curiously, using endothelial markers and stereology to measure the numbers, length, bifurcations, and total volume of capillaries, the scientists also found an age-dependent decline in angiogenesis in the same regions. The researchers proposed that a decline in angiogenesis may trigger loss of neuroplasticity without necessarily affecting neurogenesis, for example by starving new neurons of essential growth factors or nutrients.

Others were not convinced, noting that reliance on a single marker—PSA-NCAM—made the plasticity results no more than an interesting correlation. Still, Lazarov and Iadecola said the connection between age-related decline in angiogenesis and neuroplasticity was plausible. Iadecola was surprised that loss of angiogenesis did not appear to affect neurogenesis, but he noted that the donors had no obvious vascular pathology in their brains. Perhaps in people with more severe vascular problems, neurogenesis would be affected, he said.

In Grown-Up Brain, Nary a Newborn Neuron
In the Nature paper, first author Shawn Sorrells and colleagues used many of the same markers—Sox2, GFAP, DCX, and PSA-NCAM—to assess neurogenesis in postmortem samples across the lifespan. This included 11 samples from prenatal donors, the youngest of whom was only at 14 weeks gestation. They also analyzed seven samples from infants who died during their first year of life, one from a 7-year-old, one from a 13-year-old, and 17 samples from adults up to 77 years of age at the time of death. The samples came from multiple sources, and were not limited to healthy donors, or all postmortem. They included hippocampal tissue from surgical resection in 22 people with epilepsy, who ranged from three months to 64 years old.

For the postmortem samples, the researchers used three to five coronal sections to assess cell numbers. Rather than using stereology to estimate the total number of cells in the dentate gyrus, the researchers counted cells in individual sections. Three researchers independently counted each section while blinded to the age of the donor. They identified key structural landmarks, most notably the cell-dense GCL, to infer the relative locations of the cells.

In prenatal samples, the scientists found abundant proliferating Ki67+ cells that expressed the progenitor markers Sox1 and Sox2. Numbers of these cells plummeted during the first year of life, and were near zero in samples from people 7 or older. Notably, these proliferating cells never coalesced beneath the GCL to form a distinctive layer in the SGZ, a structural niche that supports neurogenesis in rodent models. The researchers confirmed the absence of this layer by electron microscopy on a subset of their samples, ranging in age from 22 gestational weeks to 48 years of age.

Neurogenesis Decline. Sections of dentate gyrus reveal a sharp decline in young neurons (yellow) from birth to 77 years of age. Granule cell layer traced in blue. [Courtesy of Sorrells et al., Nature, 2018.]


DCX+/PSA-NCAM+ cells, representing intermediate neural progenitors and immature neurons, clustered throughout the GCL at birth to a density of about 1,600 cells per mm2. In prenatal and infant samples, these cells had a smooth, elongated morphology characteristic of young neurons. By 13 years of age, sections only contained around two young neurons per mm2, or roughly one or two cells per section. Likewise, the investigators found no evidence of young neurons in samples from epilepsy patients older than 11. As for adults, none of the surgical or postmortem samples contained DCX+/PSA-NCAM+ cells, however the researchers did find cells that expressed PSA-NCAM without DCX. Unlike the elongated young neurons in infant samples, these cells had a more mature neuronal morphology with distinct axons and dendrites, and expressed NeuN, suggesting they were highly plastic neurons. The researchers also identified DCX+ cells in some older childhood and adult samples, but these cells co-expressed glial markers, and under the gaze of electron microscopy, had glial morphology.

The researchers also looked for evidence of neurogenesis in rhesus macaques. By staining with similar neuronal markers, they found that unlike in the human brain, proliferating neural progenitors did gather in the SGZ before birth. However, the number of these young neurons decreased eightfold between birth and 1.5 years of age, and were sparse in 7-year-old animals. Similarly, labeling dividing cells with BrdU revealed a steep drop-off in dividing neurons between 1.5 and 7 years of age.

Glial Impostor?
DCX+ (green) cells co-expressing the oligodendrocyte marker Olig2 (red). [Courtesy of Sorrells et al., Nature, 2018.]

The researchers concluded that neurogenesis is robust only in the earliest stages of development, and that DCX+ cells in late childhood and adult samples were actually glia. In an email to Alzforum, Sorrells and Alvarez-Buylla speculated that the cells identified as young neurons in the Boldrini study were also likely non-neuronal. “Identifying new neurons is technically challenging—in our own recent study we made similar observations to what Boldrini et al. report, but after extensive additional analysis of the shape and appearance of the cells in question, including electron microscopy and gene expression, we determined that these cells were not in fact young neurons or neural progenitors but different types of cells altogether,” they wrote.

However, Boldrini asserted that in her study, the cells stained for both DCX and PSA-NCAM did not co-localize with cells that appeared to be glia based on the pattern of Nissl staining, and were present in the thousands. Boldrini added that the immature neurons took on a pyramidal shape, characteristic of neurons, not glia.

Sorrells and Alvarez-Buylla further drew attention to the lack of a defined layer of proliferating cells in the SGZ in their study, adding that Boldrini’s samples also appeared to lack a distinct layer of cells there. In rodents, neural progenitors gather and proliferate in the SGZ. On this issue, Boldrini thinks that perhaps in humans neurogenesis occurs in a more scattered fashion. She said that for this reason, taking stock of cells throughout the entire dentate gyrus is crucial to capture these sparse cells.—Jessica Shugart

via Newborn Neurons in the Adult Brain: Real Deal, or Glial Imposters? | ALZFORUM

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[ARTICLE] Neurogenesis: Study Sparks Controversy Over Whether Humans Continue to Make New Neurons Throughout Life



A new study offers new data challenging the prevailing view that neurogenesis occurs beyond childhood into adulthood.

For two decades, humans have been comforted by scientific discoveries showing that specific regions of the human brain, primarily the hippocampus, continue to grow neurons throughout life, a finding that suggests more is better (for learning and memory that are governed by the hippocampus) and that there may be backup plans in case our old neurons die.

But scientists at the University of California, San Francisco (UCSF) have looked at dozens of tissue samples from autopsied brains and epilepsy patients undergoing resection and found that the birth of new neurons is robust in fetal life and during the first year of life but then decreases rapidly in childhood. In adults, it was not possible (with current technology used) to identify populations of new neurons. The oldest samples with evidence of neurogenesis came from seven-year-old and a thirteen-year-old, the researchers reported in the March 15 issue of Nature.

Until the late 1990s, it had long been thought that primates, including humans, are born with the complete set of neurons for a lifetime. Through development and beyond, humans lose neuronal cells, but never gain new ones. First came rodent and bird studies, then monkeys, refuting these age-old beliefs, and then evidence from humans as well.

In an editorial in the same issue of Nature, neuroscientist Jason Snyder, a doctoral candidate and assistant professor in the psychology department at the University of British Columbia, wrote that the findings “are in stark contrast to the prevailing view” and “certain to stir up controversy.”

The study was led by Arturo Alvarez-Buylla, PhD, the Heather and Melanie Muss professor of neurological surgery at the University of California, San Francisco. Dr. Alvarez-Buylla was at Rockefeller University in the 1980s working with his mentor, Fernando Nottebohm, PhD, who first reported the birth of new neurons in the brains of adult canaries and its possible link to learning their annual mating songs. Dr. Alvarez-Buylla has spent his career studying the mechanism of adult neurogenesis and began looking at human samples more than a decade ago.

“We find that neurogenesis in the adult hippocampus in humans, if it occurs at all, is an extremely rare phenomenon, raising questions about its contribution to brain repair or normal brain function,” said the neuroscientist. “We have just looked at one region of the brain. There is a lot more work to do. Clearly the fascinating process of making a new neuron continues in young children. We should continue to study how neurons are made and whether it is possible to induce new neurons to grow in the adult brain to treat brain diseases.”


Dr. Alvarez-Buylla and his colleagues studied 59 samples of human hippocampal tissue from UCSF and collaborating centers around the world. Thirty-seven came from postmortem brain samples and the rest were from fresh tissue excised from patients undergoing treatment for epilepsy. The samples came from fetuses, newborns, children, adolescents and adults. The oldest sample came from a 77-year-old.

The investigators used several techniques to tag neural stem cells and young neurons (the markers include doublecortin and PSA NCAM) to search for evidence of newborn and mature brain cells. They also used high resolution electron microscopy to examine the cell’s shape and structure to make sure they were looking at neurons and not glial cells.

Dr. Alvarez-Buylla and his colleagues found evidence of new neurons in the dentate gyrus of the hippocampus in the fetal brain tissue and in the samples from newborns and infants. They counted an average of 1,618 young neurons per square millimeter of brain tissue at birth. The older the infant, the fewer the new neurons. The tissue from one-year olds have five-fold fewer new neurons; there was a 23-fold decline by age seven, and new neurons were hard to find by adolescence. The teen brain had about 2.4 new cells per square millimeter of dentate gyrus tissue.

The investigators did find an occasional young neuron in a few adult post-mortem brain samples in the walls of the brain ventricles, as previously reported, but when looking at the hippocampus of samples from people over 18 years old, the group could not find the young neurons or much evidence of proliferation next to the dentate gyrus, said Dr. Alvarez-Buylla.

The group also looked for neural progenitor stem cells that give rise to neurons. Again, it was not surprising that the fetal brain was filled with these progenitors, particularly in regions were the dentate is growing, but these cells were gone by early childhood, he explained.

Dr. Alvarez-Buylla said that the idea for this study was sparked by a visit to the laboratory Zhengang Yang, PhD, at Fudan University in China and co-author on the current paper.

Dr. Yang showed him some beautifully stained samples of hippocampal tissue from a 35-year-old. The tissue was collected within hours of his death. “We could find some new neurons close to the walls of the ventricle, but not in the hippocampus,” said Dr. Alvarez-Buylla. That was four years ago.

Dr. Alvarez Buylla returned to California and started looking at more hippocampal tissue in samples collected at UCSF. Then, he and his colleagues looked at more tissue samples from Jose Manuel Garcia-Verdugo, PhD, of University of Valencia in Spain and from Gary W. Mathern, MD, from the University of California, Los Angeles, also study collaborators.

“We are simply reporting what we observed, and to correct the record that there is no significant neurogenesis in the adult human hippocampus,” Dr. Alvarez-Buylla said.

“The process of making a new neuron in the adult brain remains a fundamental problem that we need to understand,” added Dr. Alvarez-Buylla, who is co-founder of Neurona Therapeutics, and serves on its scientific advisory board. “What’s next is to do more research.”

He thinks that the replacement of neurons in the complex human brain could potentially change brain circuits in detrimental ways. “Neurons have the potential to live for very long periods of time. There may be important reasons why we may need to keep the neurons we develop in fetal and early postnatal development.

There could be other reasons, he explained: “Making a new neuron in large brains, like ours, may be complicated by the changes in development. We have speculated that the early specification of stem cells (that is linked to location) could make it very difficult to seed stem cells within niches that continually expand to incredibly large sizes. It could also be associated to longevity; stem cells may not be able to self-renew infinitively and in species that live as long as we do, these key progenitors may get used up in early life. We, simply, do not know why some species retain significant neurogenesis in adulthood, while others, like us don’t.”

He also stressed that this study focused only in the hippocampus and in the search for the new neurons in the dentate. “There is a lot of human brain yet to be explored.”

“I think that we need to step back and ask what that means,” added UCSF neuroscientist Shawn F. Sorrells, PhD, the first author of the Nature paper. “If neurogenesis is so rare that we can’t detect it, can it really be playing a major role in plasticity or learning and memory in the hippocampus?”


No one refutes the science that rodents continue to grow neurons throughout adulthood and that these neurons migrate to specialized regions like the dentate gyrus and the olfactory bulb. Elizabeth Gould, PhD, a neuroscientist at Princeton University, described neurogenesis in the dentate gyrus of adult rats in 1992. Fred H. Gage, PhD, a neurobiologist in the laboratory of genetics at The Salk Institute for Biological Sciences, published a series of studies suggesting that enriched environments and exercise could enhance adult neurogenesis in rats. Others showed that stress could diminish it.

Dr. Gage and his colleagues reported the first evidence of adult human neurogenesis in tissue samples from five cancer patients in 1997. Cancer doctors had used an imaging stain called bomodeoxyuridine (BrdU) in their patients to track tumor growth, and the scientists received permission to obtain brain slices right after the patients died. BrdU gets into the DNA of dividing cells, and the Salk scientists found staining in the dentate, which suggested that these were new neurons.


The science of adult neurogenesis continued to be debated as researchers questioned how robust the cellular growth is, where it is, and, most importantly, what is the purpose of this proliferation.

This new study may fuel this controversy. “This paper is the most thorough and rigorous study to date addressing human hippocampal neurogenesis,” said David R. Kornack, PhD, associate professor in the department of neuroscience at the University of Rochester. “It is such an important issue whether we continue to make new neurons in our brains as adults that the evidence has to be incontrovertible.”

Dr. Kornack has been studying neurogenesis for decades and was working with Pasko Rakic, MD, PhD, at Yale University School of Medicine, in the late 1990s when they identified evidence of adult neurogenesis in macaque monkeys — in a confocal microscope, they saw what they believed to be a small population of new neurons in the dentate gyrus of the hippocampus.

They published the study in 1999 in the Proceedings of the National Academy of Sciences, and Dr. Rakic continued to raise his concerns about adult neurogenesis in humans.

“For me, this new study closes the chapter about the prevalence of hippocampal neurogenesis in human adults,” added Dr. Kornack. “We are learning the powers and limitations of the technology and defining what a new neuron is. The strength of the finding is that they did see new neurons in younger tissue and not in older tissue. It confirms that hippocampal neurogenesis declines with age, which was already shown in monkeys and rodents. We are a long-lived species that rely on stored memories and behavior for our survival and stability. It may be a disadvantage to replace old neurons.”

His mentor agrees. “I feel vindicated,” said Pasko Rakic, MD, PhD, the Dorys McConnell Duberg professor of neuroscience and professor of neurology at Yale University School of Medicine. “I wanted to discover adult human neurogenesis, but I just couldn’t find it.”

Dr. Rakic said that adult neurogenesis is a limited event in the human brain, where even fewer new neurons were found than in the macaques. Additionally, he said adult rats had 10 to 14 times more new neurons in the hippocampus than the macaques had. The decreases in the number of these cells from rats to primates suggests, he said, “it must be more important not to have new neurons.”

Dr. Rakic added: “In evolution, our advantage is to preserve learned behavior. For memory, it isn’t productive to have new neurons but to preserve our old ones. We need stability of our neurons. If we added new neurons, they would not hold the memories of our past experiences. I use the same neurons I did as a child when I think of my mother. We need to invest in understanding how to keep our old neurons healthy. People think this is a negative finding. I think it is positive. It shows the value of keeping old cells in our brain, cells that have accumulated a lifetime of knowledge.”

Dr. Gage, PhD, of the Salk Institute for Biological Sciences, said that this latest study doesn’t disprove adult neurogenesis. Their conclusion is based “on the absence of morphological features and the lack of expression of two marker proteins, DCX and PSA-NCAM,” he said. “Both markers are very sensitive to methodological factors inherent to human brain tissue. One is the postmortem delay, the time between the death of a person and the moment the brain is removed and fixed. DCX is rapidly broken down after death and its staining disappears within a few hours of postmortem delay.”

He continued: “In this paper, many subjects had very long postmortem delays of ‘less than 48 hrs.’ As there is no mention of matching between subjects, or other optimization done in terms of the markers used, this influence of postmortem delay and on DCX integrity, which will also differ strongly between subjects, would question their conclusion about neurogenesis, as no control for DCX degradation was included.”

He added that adult mouse and adult human neurogenesis may use different proteins and they did not quantify or measure adult neurogenesis but rather proteins expressed in mice and immature cells.


•. Sorrells SF, Paredes MR, Cebrian-Silla A, et al Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults 2018; 555(7696): 377–381.

•. Snyder JS. Questioning human neurogenesis 2018; 555(7696):315–316.

•. Kornack DR, Rakic P. Continuation of neurogenesis in the hippocampus of the adult macaque monkey Natl Acad Sci USA 1999; 96(10):5768–5773.

© 2018 American Academy of Neurology


via Neurogenesis: Study Sparks Controversy Over Whether Humans C… : Neurology Today

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[WEB SITE] New brain cells are added in elderly adult brains too

According to a new study from the Columbia University however, brain cells are continuously added to our brains even when we reach our 70s. This is a process called neurogenesis. Their work is published in a study that appeared in the latest issue of the journal Cell Stem Cell this week.

Neuron detailed anatomy illustrations. Neuron types, myelin sheath formation, organelles of the neuron body and synapse. Image Credit: Tefi / Shutterstock

Lead author Dr. Maura Boldrini, a research scientist at the department of psychiatry, Columbia University and her colleagues investigated the brains of 28 dead people aged between 14 and 79 years. They were studying the effects of aging on the brain’s neuron production. The team examined the brains that were donated by the families of the deceased at the time of death. The brains were frozen immediately at minus-112 degrees Fahrenheit before they could be examined. This preserved the tissues.

Neurogenesis has been shown to decline with age in lab mice and rats as well as in experimental primates. The team wanted to explore if same rates of decline are seen in human brains as well. So they checked the brains samples for developing neurons. These developmental stages included stem cells, intermediate progenitor cells, immature neuronal cells and finally new mature neurons. They focused on the hippocampus region of the brain that deals with memory and emotional control and behavior.

The results revealed that for all age groups, the hippocampus shows new developing neurons. The researchers concluded that even during old age, the hippocampus continues to make new neurons. The differences that they noted with age include reduction in the development of new blood vessels as people got older. The proteins that help the neurons to make new connections are reduced with age. This was a finding that differentiated ageing brains from younger ones, they explained. Boldrini said the new neurons are there in older brains but they make fewer connections than younger brains. This explains the memory losses and decrease in emotional resiliency in older adults she said.

An earlier study last month came from another set of researchers led by University of California San Francisco researcher Arturo Alvarez-Buylla. The study titled, “Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults,” was published first week of March this year in the journal Nature.

The team found that after adolescence there is little or no neurogenesis in the brain. They examined the brains of 17 deceased individuals and 12 patients with epilepsy part of whose brains had been surgically resected. The debate between the two teams continues. Boldrini explained that Buylla’s team had examined different types of samples that were not preserved as her samples had been.

Further the other team examined three to five sections of the hippocampus and not the whole of it she explained. More studies on this needed to make concrete conclusions regarding neurogenesis in the elderly say experts.


via New brain cells are added in elderly adult brains too

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[WEB SITE] Brain tissue samples suggest we stop adding neurons in our early teens

By Deborah Netburn – Los Angeles Times, Posted: 12:00 a.m. Saturday, March 17, 2018

New research suggests that the human brain does not add more neurons to its circuitry once it has reached maturity.

The work, published in Nature, contradicts a smattering of earlier studies that found that humans did indeed have the ability to add to their neural networks even after they reached adulthood.

Amar Sahay, a professor at the Harvard Stem Cell Institute who was not involved in the research, said the new findings are sure to make a splash.

“But that’s science,” he said. “It’s not always a straight line from point A to point B. Sometimes it’s a winding road.”

Researchers have known for decades that many animals — including mice, canaries and monkeys — have the ability to produce new neurons over the course of their lives in the process known as neurogenesis.

A small number of papers had indicated that adult humans also possessed this capability, specifically in an interior region of the brain known as the hippocampus that is associated with memory.

However, after examining brain tissue samples collected from 59 human subjects ranging in age from a 14-week-old fetus to a 77-year-old man, the authors found that neurogenesis drops off considerably in humans after one year of life. After adolescence, it appears to stop completely.

The findings came as a bit of a shock to the research team from the University of California, San Francisco

“We went into this work thinking we were going to find evidence of neurogenesis because other groups did,” said Mercedes Paredes, an assistant professor of neurology at UCSF and one of the leaders of the study. “So we were actually surprised when we didn’t see any evidence of it in our adult samples.”

Neurons are the oddly shaped cells that process and transmit information in our brain. Arturo Alvarez-Buylla, the principal investigator of the study, described them as the semiconductors of the brain.

The vast majority of neurons are generated during fetal development, but scientists have shown that in some regions of the brain, new neurons can continue to be made in adult animals.

“It is really a feat of biology,” said Alvarez-Buylla. “The cell has to be born, then migrate and integrate into the tissue, make new extensions to connect with other cells, and then it has to contribute to the brain function.”

Although this process has been well studied in mice, rats and canaries among other animals, only a handful of studies have sought to discover if neurogenesis also occurs in people after childhood.

“It’s tricky,” Paredes said. “It’s hard to study human brain tissue, not only to get the samples, but to know how to analyze them and have confidence in the result.”

The samples used in this work were collected from hospitals in China, Spain, Los Angeles and San Francisco. Most of the brain tissue came from people who had just died, but 22 samples came from brain operations that were performed on living people as a treatment for epilepsy.

“In those cases we were able to get the tissue very quickly, preserve them in the best way possible and then analyze them with less concern for degradation,” Paredes said.

Instead of looking for new neurons themselves, the authors analyzed their tissue samples for combinations of proteins that are associated both with young neurons and with the stem cells that would make new neurons.

To make sure there was no mistake with their detection method, the authors looked to see if they could find evidence of new neuron growth in the brain tissue of fetuses, where they were certain that new neurons were developing. And indeed, when they looked at the fetal hippocampus, they were able to see that it was filled with young neurons.

Next they wondered if perhaps their methods were only capable of detecting neurogenesis in young brains, and not in the brains of adults. To see if that was the case they analyzed two post-mortem autopsy samples and looked for evidence of young neurons in another region of the brain that is known to produce new neurons into childhood. There, the authors did find rare examples of young neurons, but very few.

After they were convinced that there was nothing wrong with their detection technique, the authors set about making sense of their data.

Their research had shown that there are significantly fewer immature neurons in the 1-year-old brain, compared to earlier stages of life. In addition, the oldest sample where they still saw evidence of young neurons came from a 13-year-old.

via Brain tissue samples suggest we stop adding neurons in our early teens

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[BLOG POST] Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?

Scientists have known for about two decades that some neurons – the fundamental cells in the brain that transmit signals – are generated throughout life. But now a controversial new study from the University of California, San Francisco, casts doubt on whether many neurons are added to the human brain after birth.

As a translational neuroscientist, this work immediately piqued my interest. It has direct implications for the research my lab does: We transplant young neurons into damaged brain areas in mice in an attempt to treat epileptic seizures and the damage they’ve caused. Like many labs, part of our work is based on a foundational belief that the hippocampus is a brain region where new neurons are born throughout life.

If the new study is right, and human brains for the most part don’t add new neurons after infancy, researchers like me need to reconsider the validity of the animal models we use to understand various brain conditions – in my case temporal lobe epilepsy. And I suspect other labs that focus on conditions including drug addiction, depression and post-traumatic stress disorder are thinking about what the UCSF study means for their investigations, too.

In the brain of a baby who died soon after birth, there are many new neurons (green in this image) in the hippocampus. Sorrells et alCC BY-ND

When and where are new neurons born?

No doubt, the adult human brain is able to learn throughout life and to change and adapt – a capability brain scientists call neuroplasticity, the brain’s ability to reorganize itself by rewiring connections. Yet, a central dogma in the field of neuroscience for nearly 100 years had been that a child is born with all the neurons she will ever have because the adult brain cannot regenerate neurons.

Just over half a century ago, researchers devised a way to study proliferation of cells in the mature brain, based on techniques to incorporate a radioactive label into new cells as they divide. This approach led to the startling discovery in the 1960s that rodent brains actually could generate new neurons.

Neurogenesis – the production of new neurons – was previously thought to only occur during embryonic life, a time of extremely rapid brain growth and expansion, and the rodent findings were met with considerable skepticism. Then researchers discovered that new neurons are also born throughout life in the songbird brain, a species scientists use as a model for studying vocal learning. It started to look like neurogenesis plays a key role in learning and neuroplasticity – at least in some brain regions in a few animal species.

Even so, neuroscientists were skeptical that many nerve cells could be renewed in the adult brain; evidence was scant that dividing cells in mammalian brains produced new neurons, as opposed to other cell types. It wasn’t until researchers extracted neural stem cells from adult mouse brains and grew them in cell culture that scientists showed these precursor cells could divide and differentiate into new neurons. Now it is generally well accepted that neurogenesis takes place in two areas of the adult rodent brain: the olfactory bulbs, which process smell information, and the hippocampus, a region characterized by neuroplasticity that is required for forming new declarative memories.

Adult neural stem cells cluster together in what scientists call niches – hotbeds for cultivating the birth and growth of new neurons, recognizable by their distinctive architecture. Despite the mounting evidence for regional growth of new neurons, these studies underscored the point that the adult brain harbors only a few stem cell niches and their capacity to produce neurons is limited to just a few types of cells.

With this knowledge, and new tools for labeling proliferating cells and identifying maturing neurons, scientists began to look for postnatal neurogenesis in primate and human brains.

What’s happening in adult human brains?

Many neuroscientists believe that by understanding the process of adult neurogenesis we’ll gain insights into the causes of some human neurological disorders. Then the next logical step would be trying to develop new treatments harnessing neurogenesis for conditions such as Alzheimer’s disease or trauma-induced epilepsy. And stimulating resident stem cells in the brain to generate new neurons is an exciting prospect for treating neurodegenerative diseases.

Because neurogenesis and learning in rodents increases with voluntary exercise and decreases with age and early life stress, some workers in the field became convinced that older people might be able to enhance their memory as they age by maintaining a program of regular aerobic exercise.

However, obtaining rigorous proof for adult neurogenesis in the human and primate brain has been technically challenging – both due to the limited experimental approaches and the larger sizes of the brains, compared to reptiles, songbirds and rodents.

Researchers injected a compound found in DNA, nicknamed BrdU to identify brand new neurons in human adult hippocampus – but the labeled cells were extremely rare. Other groups demonstrated that adult human brain tissue obtained during neurosurgery contained stem cell niches that housed progenitor cells that could generate new neurons in the lab, showing that these cells had an inborn neurogenic capacity, even in adults.

But even when scientists saw evidence for new neurons in the brain, they tended to be scarce. Some neurogenesis experts were skeptical that evidence based on incorporating BrdU into DNA was a reliable method for proving that new cells were actually being born through cell division, rather than just serving as a marker for other normal cell functions.

Further questions about how long human brains retain the capacity for neurogenesis arose in 2011, with a study that compared numbers of newborn neurons migrating in the olfactory bulbs of infants versus older individuals up to 84 years of age. Strikingly, in the first six months of life, the baby brains contained lots of chains of young neurons migrating into the frontal lobes, regions that guide executive function, long-range planning and social interactions. These areas of the human cortex are hugely increased in size and complexity compared to rodents and other species. But between 6 to 18 months of age, the migrating chains dwindled to a thin stream. Then, a very different pattern emerged: Where the migrating chains of neurons had been in the infant brain, a cell-free gap appeared, suggesting that neural stem cells become depleted during the first six months of life.

Questions still lingered about the human hippocampus and adult neurogenesis as a source for its neuroplasticity. One group came up with a clever approach based on radiocarbon dating. They measured how much atmospheric ¹⁴C – a radioactive isotope derived from nuclear bomb tests – was incorporated into people’s DNA. This method suggested that as many as 700 new cells are added to the adult human hippocampus every day. But these findings were contradicted by a 2016 study that found that the neurogenic cells in the adult hippocampus could only produce non-neuronal brain cells called microglia.

Rethinking neurogenesis research

Now the largest and most comprehensive study conducted to date presents even stronger evidence that robust neurogenesis doesn’t continue throughout adulthood in the human hippocampus – or if it does persist, it is extremely rare. This work is controversial and not universally accepted. Critics have been quick to cast doubt on the results, but the finding isn’t totally out of the blue.

So where does this leave the field of neuroscience? If the UCSF scientists are correct, what does that mean for ongoing research in labs around the world?

Because lots of studies of neurological diseases are done in mice and rats, many scientists are invested in the possibility that adult neurogenesis persists in the human brain, just as it does in rodents. If it doesn’t, how valid is it to think that the mechanisms of learning and neuroplasticity in our model animals are comparable to those in the human brain? How relevant are our models of neurological disorders for understanding how changes in the hippocampus contribute to disorders such as the type of epilepsy I study?

In my lab, we transplant embryonic mouse or human neurons into the adult hippocampus in mice, after damage caused by epileptic seizures. We aim to repair this damage and suppress seizures by seeding the mouse hippocampus with neural stem cells that will mature and form new connections. In temporal lobe epilepsy, studies in adult rodents suggest that naturally occurring hippocampal neurogenesis is problematic. It seems that the newborn hippocampal neurons become highly excitable and contribute to seizures. We’re trying to inhibit these newborn hyperexcitable neurons with the transplants. But if humans don’t generate new hippocampal neurons, then maybe we’re developing a treatment in mice for a problem that has a different mechanism in people.

Perhaps our species has evolved separate mechanisms for neuroplasticity, distinct from those used by species such as rats and mice. One possibility is that there are other sites in the human brain where neurogenesis occurs – its a big structure and more exploration will be necessary. If it turns out to be true that the human brain has a diminished capacity for neurogenesis after birth, the finding will have important implications for how neuroscientists like me think about tackling brain disorders.

Perhaps most importantly, this work underscores how crucial it is to learn how to increase the longevity of the neurons we do have, born early in life, and how we might replace or repair neurons that become damaged.

via Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?


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[BLOG POST] 10 Proven Ways To Grow Your Brain: Neurogenesis And Neuroplasticity

Scientists once thought the brain stopped developing after the first few years of life. But new research has shown that the brain can form new neural pathways and create neurons even in adulthood (Neuroplasticity and Neurogenesis).

Exercise for 30 minutes per day or meditation stimulates the production of new synapses; eating foods rich in flavonoids (cocoa and blueberries) and antioxidants (green tea) also helps with brain growth. In addition to these, here are ten proven ways to promote neurogenesis and neuroplasticity in your brain:

[Download free infographic below]

1. Intermittent Fasting 

Calorie-restriction/fasting increases synaptic plasticity, promotes neuron growth, decreases risk of neurodegenerative diseases, and improves cognitive function according to the Society for Neuroscience.

During fasting, a metabolic shift lowers the body’s leptin levels, a hormone produced by fat. As a result, the brain receives a chemical signal for neurons to produce more energy.

Popular methods include: fasting one day per week, for an entire 24-hour period; a 16-hour fast — having your last meal at 8pm and breaking your fast at lunch (12pm) the next day; the “5-2” model — five days of regular eating and two days (non-consecutive) of calorie-restricted eating in a week (between 400-600 calories).

2. Travel

Traveling promotes neurogenesis by exposing your brain to new, novel, and complex environments. Paul Nussbaum, a neuropsychologist from the University of Pittsburgh explains, “Those new and challenging situations cause the brain to sprout dendrites.”

You don’t need to travel across the world to reap these benefits either; taking a weekend road trip to a different city gives your brain the same stimulation.

3. Use Mnemonic Devices

Memory training promotes connectivity in your brain’s prefrontal parietal network and can slow memory loss with age. Mnemonic devices are a form of memory training that combines visualization, imagery, spatial navigation, and rhythm and melody.

A popular technique is known as the Method of Loci (MoL). Explained by Scientific American: It involves visualizing a familiar route — through a building, your home, or your way to work — and placing items to be remembered at attention-grabbing spots along the way. The more bizarre you make these images, the better you will recall them later. By simply retracing your steps, like a fishing line, you will “pull up” items to the surface. Along with objects, numbers, and names, this method has helped people with depression store happy memories that they can retrieve in times of stress.

Begin using mnemonic techniques and engage in memory training; start working on remembering names, scriptures, or poems. Here are some mnemonic techniques to get you started.

4. Learn an Instrument

Brain scans on musicians show heightened connectivity between brain regions. Neuroscientists explain that playing a musical instrument is an intense, multi-sensory experience. The association of motor actions with specific sounds and visual patterns leads to the formation of new neural networks.

If you’ve always wanted to learn an instrument, consider brain growth as a motivator to get you started.

5. Non-Dominant Hand Exercises

Using your non-dominant hand to do simple tasks such as brushing your teeth, texting, or stirring your coffee/tea can help you form new neural pathways. These cognitive exercises, also known as “neurobics,” strengthen connectivity between your brain cells. “It’s like having more cell towers in your brain to send messages along. The more cell towers you have, the fewer missed calls,” explains Dr. P. Murali Doraiswamy, chief of biological psychiatry at Duke University Medical Center.

Studies have also shown that non-dominant hand activities improves your emotional health and impulse control. Switch hands with simple tasks to give you brain a workout.

6. Read Fiction

A study conducted over 19 consecutive days by Emory University showed increased and ongoing connectivity in the brains of participants after they all read the same novel. Researcher Gregory Berns, noted, “Even though the participants were not actually reading the novel while they were in the scanner, they retained this heightened connectivity.”

Enhanced brain activity was observed in the region that controls physical sensations and movement systems. Berns explains that reading a novel “can transport you into the body of the protagonist.” This ability to shift into another mental state is a crucial skill for mastering the complex social relationships. Add some novels to your reading list for these extra brain benefits.

7. Expand your Vocabulary 

Learning new words activates the brain’s visual and auditory processes (seeing and hearing a word) and memory processing. A small vocabulary is linked with poor cognitive efficiency in children, while an expansive vocabulary is an indicator of student success.

Learn one new word each day to expand your vocabulary and give your brain a workout. Use apps or online courses to make it fun.

8. Create Artwork

In a journal article titled, “How Art Changes Your Brain,” participants in a 10-week art course (a two hour session, one day per week) showed enhanced connectivity of the brain at a resting state known as the “default mode network” (DMN). The DMN influences mental processes such as introspection, memory, and empathy. Engaging in art also strengthens the neural pathway that controls attention and focus.

Whether it’s creating mosaics, jewelry, pottery, painting, or drawing, the combination of motor and cognitive processing will promote better brain connectivity. Join a local art class; just once a week will help your brain grow.

9. Hit the Dance Floor 

Not many of us would think of dancing as a “decision-making process,” but that’s the reason why it’s healthy for your brain. Especially free-style dancing and forms that don’t retrace memorized paths. Researchers compared the effectiveness of cognitive activities in warding off Alzheimer’s and dementia and found that dancing had the greatest effect (76% risk reduction); higher than doing crossword puzzles at least four days a week (47%) and reading (35%).

Dancing increases neural connectivity because it forces you to integrate several brain functions at once —kinesthetic, rational, musical, and emotional. If you’re dancing with a partner, learning both “Lead” and “Follow” roles will increase your cognitive stimulation.

10. Sleep

Studies from NYU showed that sleep helps learning retention with the growth of dendritic spines, the tiny protrusions that connect brain cells and facilitates the passage of information across synapses.

Aim for 7-8 hours of sleep each night. If you’re struggling to get a consistently good sleep, try creating a nightly ritual; going to bed at the same time; drinking some sleep-inducing tea; or making your room as dark as possible.

Infographic created by VisMe.
For more of Thai’s articles on strategic living, visit The Utopian Life. Connect with him on FB and Twitter.
10 Proven Ways to Grow Your Brain Neurogenesis & Neuroplasticity

Source: 10 Proven Ways To Grow Your Brain: Neurogenesis And Neuroplasticity | HuffPost

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[BLOG POST] How to Make New Brain Cells and Improve Brain Function

Scientists used to believe that the brain stopped making new brain cells past a certain age. But that believe changed in the late 1990’s as a result of several studies which were performed on mice at the Salk Institute.

After conducting maze tests, neuroscientist Fred H. Gage and his colleagues examined brain samples collected from mice. What they found challenged long standing believes held about neurogenesis, or the creation of new neurons.

To their astonishment, they discovered that the mice were creating new neurons. Their brains were regenerating themselves.

All of the mice showed evidence of neurogenesis but the brains of the athletic mice showed even more.

 These mice, the ones that scampered on running wheels, were producing two to three times as many new neurons as the mice that didn’t exercise.

The difference between the mice who performed well on the maze tests and those that floundered was exercise.

That’s great for the mice, but what about humans?

To find out if neurogensis occurred in adult humans, Gage and his colleagues obtained brain tissue from deceased cancer patients who had donated their bodies to research. While still living, these people were injected with the same type of compound used on Gage’s mice to detect new neuron growth. When Gage dyed their brain samples, he saw new neurons. Like in the mice study, they found evidence of neurogenesis – the growth of new brain cells.

From the mice study, it appears that those who exercise produce even more new brain cells than those who don’t. Several studies on humans seem to suggest the same thing.

Studies performed at both the University of Illinois at Urbana- Champaign and Columbia University in New York City have shown that exercise benefits brain function. The test subjects were given aerobic exercises such as walking for at least one hour three times a week. After 6 months they showed significant improvements in memory as measured by a word-recall test. Using fMRI scans they also showed increases in blood flow to the hippocampus (part of the brain associated with memory and learning). Scientists suspect that the blood pumping into that part of the brain was helping to produce fresh neurons.

Dr. Patricia A. Boyle and her colleagues of Rush Alzheimer’s Disease Center in Chicago found that the greater a person’s muscle strength, the lower their likelihood of being diagnosed with Alzheimer’s. The same was true for the loss of mental function that often precedes full-blown Alzheimer’s.

Neuroscientist Gage, by the way, exercises just about every day, as do most colleagues in his field. As Scott Small a neurologist at Columbia explains,

 I constantly get asked at cocktail parties what someone can do to protect their mental functioning. I tell them, ‘Put down that glass and go for a run.

So if you want to grow some new brain cells and improve your brain function, go get some exercise!

Source: How to Make New Brain Cells and Improve Brain Function | Online Brain Games Blog

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[WEB SITE] This FDA Approved Drug Could Permanently Repair Brain Damage in Stroke Victims

  • Using a drug already approved for clinical trials, researchers were able to reduce brain damage and boost the growth of new brain cells in mice suffering from strokes.
  • The research offers new hope to those dealing with the aftermath of strokes, which are the fifth leading cause of death in the United States.


Researchers from the University of Manchester have developed a new treatment that could limit the damage caused by strokes and also promote repair in the affected area of the brain. What’s more, the drug they’re using has already been clinically approved.

The researchers’ study is published in Brain, Behavior and Immunityand it recounts how they developed their treatment using mice bred to develop ischemic strokes, the most prevalent type of stroke and one that occurs when an artery that supplies oxygen-rich blood to the brain is blocked. Soon after the mice experienced a stroke, the researchers treated them with interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory drug that is already licensed for use in treating rheumatoid arthritis.

They noticed a reduction in the amount of brain damage typically observed after a stroke and also noted that the drug boosted neurogenesis (the birth of new cells) in the areas that did experience brain damage in the days following the treatment. The mice even regained the motor skills they lost due to the stroke.


Stroke is the fifth leading cause of death in the United States and about 800,000 people suffer from one each year, according to the Centers for Disease Control and Prevention (CDC). They occur when the flow of blood to the brain is interrupted, usually due to a blood clot or a buildup of fat that broke off from the arteries and traveled to the brain. The condition is extremely dangerous because brain cells can die within a few minutes of the stroke, causing permanent damage or even death.

We still don’t have a treatment to adequately prevent or reverse the damage to the brain caused by strokes, but the Manchester researchers believe that their development could change that. Though they are still in early stages of clinical trials, they hope to eventually move on to larger trials and eventually human testing. Together with other research, this new study offers hope to the thousands of people whose lives are impacted by strokes worldwide.

Source: This FDA Approved Drug Could Permanently Repair Brain Damage in Stroke Victims

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[WEB SITE] How Do Neuroplasticity and Neurogenesis Rewire Your Brain? – Psychology Today

Source: XStudio3D/Shutterstock

For over a decade, neuroscientists have been trying to figure out how neurogenesis (the birth of new neurons) and neuroplasticity (the malleability of neural circuits) work together to reshape how we think, remember, and behave.

This week, an eye-opening new study, “Adult-Born Neurons Modify Excitatory Synaptic Transmission to Existing Neurons” reported how newborn neurons (created via neurogenesis) weave themselves into a “new and improved” neural tapestry. The January 2017 findings were published in the journal eLife.

During this state-of-the-art study on mice, neuroscientists at the University of Alabama at Birmingham (UAB) found that the combination of neurogenesis and neuroplasticity caused less-fit older neurons to fade into oblivion and die off as the sprightly, young newborn neurons took over existing neural circuits by making more robust synaptic connections.

For their latest UAB study, Linda Overstreet-Wadiche and Jacques Wadiche—who are both associate professors in the University of Alabama at Birmingham Department of Neurobiology—focused on neurogenesis in the dentate gyrus region of the hippocampus.

The dentate gyrus is an epicenter of neurogenesis responsible for the formation of new episodic memories and the spontaneous exploration of novel environments, among other functions.

More specifically, the researchers focused on newly born granule cell neurons in the dentate gyrus that must become wired into a neural network by forming synapses via neuroplasticity in order to stay alive and participate in ongoing neural circuit function.

There are only two major brain regions that are currently believed to have the ability to continually give birth to new neurons via neurogenesis in adults; one is the hippocampus (long-term and spatial memory hub) the second is the cerebellum (coordination and muscle memory hub). Notably, granule cells have the highest rate of neurogenesis. Both the hippocampus and cerebellum are packed, chock-full with granule cells.

Interestingly, moderate to vigorous physical activity (MVPA) is one of the most effective ways to stimulate neurogenesis and the birth of new granule cells in the hippocampus and the cerebellum. (As a cornerstone of The Athlete’s Way platform, I’ve been writing about the link between MVPA and neurogenesis for over a decade. To read a wide range of Psychology Today blog posts on the topic click on this link.)

Drawing of Purkinje cells (A) and granule cells (B) from pigeon cerebellum by Santiago Ramón y Cajal, 1899. Source: Instituto Santiago Ramón y Cajal, Madrid, Spain

Granule cells were first identified by Santiago Ramón y Cajal, who made beautiful sketches in 1899 that illustrate how granule cells create synaptic connections with Purkinje cells in the cerebellum. His breathtaking and Nobel Prize-winning illustrations are currently on a museum tour across the United States (on loan from the Instituto Santiago Ramón y Cajal in Madrid, Spain) as part of “The Beautiful Brain” traveling art exhibit.

(As a side note, the olfactory bulb is the only other subcortical brain area known to have high rates of neurogenesis. Speculatively, this could be one reason that scent plays such an indelible and ever-changing role in our memory formation and ‘remembrance of things past.’)

Neurogenesis and Neuroplasticity Work Together to Rewire Neural Circuitry

One of the key aspects of neural plasticity is called Neural Darwinism, or “neural pruning,” which means that any neuron that isn’t ‘fired-and-wired’ together into a network is likely to be extinguished. The latest UAB research suggests that newborn neurons play a role in expediting this process by “winning out” in a survival of the fittest type of neuronal battle against their more elderly or worn out counterparts.

Long before there were neuroscientific studies on neuroplasticity and neurogenesis, Henry David Thoreau unwittingly described the process of how the paths that one’s mind travels can become hardwired (when you get stuck in a rut) by describing a well-worn path through the woods. In Walden, Thoreau writes,

“The surface of the earth is soft and impressible by the feet of men; and so with the paths which the mind travels. How worn and dusty, then, must be the highways of the world, how deep the ruts of tradition and conformity!”

From a psychological standpoint, the latest UAB discovery presents the exciting possibility that when adult-born neurons weave into existing neural networks that new memories are created and older memories may be modified.

Through neurogenesis and neuroplasticity, it may be possible to carve out a fresh and unworn path for your thoughts to travel upon. One could speculate that this process opens up the possibility to reinvent yourself and move away from the status quo or to overcome past traumatic events that evoke anxiety and stress. Hardwired fear-based memories often lead to avoidance behaviors that can hold you back from living your life to the fullest.

Future Research on Neurogenesis Could Lead to New PTSD Treatments

Granule cells in the dentate gyrus are part of a neural circuit that processes sensory and spatial input from other areas of the brain. By integrating sensory and spatial information, the dentate gyrus has the ability to generate unique and detailed memories of an experience.

Before this study, Overstreet-Wadiche and her UAB colleagues had a few basic questions about how the newly born granule cells in the dentate gyrus function. They asked themselves two specific questions:

  1. Since the number of neurons in the dentate gyrus increases by neurogenesis while the number of neurons in the cortex remains the same, does the brain create additional synapses from the cortical neurons to the new granule cells?
  2. Or do some cortical neurons transfer their connections from mature granule cells to the new granule cells?

Through a series of complex experiments with mice, Overstreet-Wadiche et al. found that some of the cortical neurons in the cerebral cortex transferred all of their former connections with older granule cells (that may have been worn out or past their prime) to the freshly born granule cells that were raring to go.

This revolutionary discovery opens the door to examine how the redistribution of synapses between old and new neurons helps the dentate gyrus stay up to date by forming new connections.

One of the key questions the researchers want to dive deeper into during upcoming experiments is: “How does this redistribution relate to the beneficial effects of exercise, which is a natural way to increase neurogenesis?”

In the future, it’s possible that cutting-edge research on neurogenesis and neuroplasticity could lead to finely-tuned neurobiological treatments for ailments such as post-traumatic stress disorder (PTSD) and dementia. In a statement to UAB, Overstreet-Wadiche said,

“Over the last 10 years there has been evidence supporting a redistribution of synapses between old and new neurons, possibly by a competitive process that the new cells tend to ‘win.’ Our findings are important because they directly demonstrate that, in order for new cells to win connections, the old cells lose connections.

So, the process of adult neurogenesis not only adds new cells to the network, it promotes plasticity of the existing network. It will be interesting to explore how neurogenesis-induced plasticity contributes to the function of this brain region.

Neurogenesis is typically associated with improved acquisition of new information, but some studies have also suggested that neurogenesis promotes ‘forgetting’ of existing memories.”

Aerobic Exercise Is the Most Effective Way to Stimulate Neurogenesis and Create Adult-Born Neurons

For the past 10 years, the actionable advice I’ve given in The Athlete’s Way has been rooted in the belief that through the daily process of working out anyone can stimulate neurogenesis and optimize his or her mindset and outlook on life via neuroplasticity.

“The Athlete’s Way” program is designed to reshape neural networks and optimize your mindset. Since the beginning, this program has been based on the discovery that aerobic activity produces brain-derived neurotrophic factor (BDNF) and stimulates the birth of new neurons through neurogenesis. I describe my philosophy in the Introduction to The Athlete’s Way,

“Shifting the focus from thinner thighs to stronger minds makes this exercise book unique. The Athlete’s Way does not focus just on sculpting six-pack abs or molding buns of steel. We are more interested in bulking up your neurons and reshaping your synapses to create an optimistic, resilient, and determined mindset. The goal is transformation from the inside out.

My mission is to get this message to you so that you can use neurobiology and behavioral models to help improve your life through exercise. I am a zealot about the power of sweat to transform people’s lives by transforming their minds. My conviction is strong and authentic because I have lived it.”

I created The Athlete’s Way along with the indispensable help of my late father, Richard Bergland, who was a visionary neuroscientist, neurosurgeon, and author of The Fabric of Mind (Viking).

A decade ago, when I published The Athlete’s Way: Sweat and the Biology of Bliss (St. Martin’s Press) I put neurogenesis and neuroplasticity in the spotlight. At the time, the discovery of neurogenesis was brand new, and still a radical notion in mainstream neuroscience.

In the early 21st century, most experts still believed that human beings were born with all the neurons they would have for their entire lifespan. If anything, it was believed that people could only lose neurons or “kill brain cells” as we got older.

Understandably, when I published The Athlete’s Way in 2007 there were lots of skeptics and naysayers who thought my ideas about reshaping mindset using a combination of neurogenesis and neuroplasticity through moderate to vigorous physical activity were ludicrous.

For the past 10 years, I’ve kept my antennae up and my finger on the pulse of all the latest research on neurogenesis and neuroplasticity hoping to find additional empirical evidence that gives more scientific credibility to my system of belief and The Athlete’s Way methodology.

Needless to say, I was over the moon and ecstatic this morning when I read about the new research by Linda Overstreet-Wadiche and Jacques Wadiche that pinpoints the specifics of how adult-born neurons modify existing neural circuits. This is fascinating stuff!

These are exciting times in neuroscience. Modern day neuroscientific techniques are poised to solve many more riddles regarding the complex mechanism by which neurogenesis and neuroplasticity work together as a dynamic duo to reshape our neural networks and functional connectivity between brain regions. Stay tuned for future empirical evidence and scientific research on neurogenesis and neuroplasticity in the months and years ahead.

In the meantime, if you’d like to read a free excerpt from The Athlete’s Way that provides some simple actionable advice and practical ways for you to stimulate neurogenesis and rewire your brain via neuroplasticity and moderate to vigorous physical activity—check out these pages from a section of my book titled: Neuroplasticity and Neurogenesis: Combining Neuroscience and Sport.”


Elena W Adlaf, Ryan J Vaden, Anastasia J Niver, Allison F Manuel, Vincent C Onyilo, Matheus T Araujo, Cristina V Dieni, Hai T Vo, Gwendalyn D King, Jacques I Wadiche, Linda Overstreet-Wadiche. Adult-born neurons modify excitatory synaptic transmission to existing neurons. eLife, 2017; 6 DOI: 10.7554/eLife.19886

Source: How Do Neuroplasticity and Neurogenesis Rewire Your Brain? | Psychology Today

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