Posts Tagged hippocampus

[WEB SITE] The Adult Brain Does Grow New Neurons After All, Study Says

Study points toward lifelong neuron formation in the human brain’s hippocampus, with implications for memory and disease

The Adult Brain Does Grow New Neurons After All, Study Says

Cerebral cortical neuron. Credit: Getty Images

If the memory center of the human brain can grow new cells, it might help people recover from depression and post-traumatic stress disorder (PTSD), delay the onset of Alzheimer’s, deepen our understanding of epilepsy and offer new insights into memory and learning. If not, well then, it’s just one other way people are different from rodents and birds.

For decades, scientists have debated whether the birth of new neurons—called neurogenesis—was possible in an area of the brain that is responsible for learning, memory and mood regulation. A growing body of research suggested they could, but then a Nature paper last year raised doubts.

Now, a new study published today in another of the Nature family of journals—Nature Medicine—tips the balance back toward “yes.” In light of the new study, “I would say that there is an overwhelming case for the neurogenesis throughout life in humans,” Jonas Frisén, a professor at the Karolinska Institute in Sweden, said in an e-mail. Frisén, who was not involved in the new research, wrote a News and Views about the study in the current issue of Nature Medicine.

Not everyone was convinced. Arturo Alvarez-Buylla was the senior author on last year’s Nature paper, which questioned the existence of neurogenesis. Alvarez-Buylla, a professor of neurological surgery at the University of California, San Francisco, says he still doubts that new neurons develop in the brain’s hippocampus after toddlerhood.

“I don’t think this at all settles things out,” he says. “I’ve been studying adult neurogenesis all my life. I wish I could find a place [in humans] where it does happen convincingly.”

For decades, some researchers have thought that the brain circuits of primates—including humans—would be too disrupted by the growth of substantial numbers of new neurons. Alvarez-Buylla says he thinks the scientific debate over the existence of neurogenesis should continue. “Basic knowledge is fundamental. Just knowing whether adult neurons get replaced is a fascinating basic problem,” he said.

New technologies that can locate cells in the living brain and measure the cells’ individual activity, none of which were used in the Nature Medicinestudy, may eventually put to rest any lingering questions.

A number of researchers praised the new study as thoughtful and carefully conducted. It’s a “technical tour de force,” and addresses the concerns raised by last year’s paper, says Michael Bonaguidi, an assistant professor at the University of Southern California Keck School of Medicine.

The researchers, from Spain, tested a variety of methods of preserving brain tissue from 58 newly deceased people. They found that different methods of preservation led to different conclusions about whether new neurons could develop in the adult and aging brain.

Brain tissue has to be preserved within a few hours after death, and specific chemicals used to preserve the tissue, or the proteins that identify newly developing cells will be destroyed, said Maria Llorens-Martin, the paper’s senior author. Other researchers have missed the presence of these cells, because their brain tissue was not as precisely preserved, says Llorens-Martin, a neuroscientist at the Autonomous University of Madrid in Spain.

Jenny Hsieh, a professor at the University of Texas San Antonio who was not involved in the new research, said the study provides a lesson for all scientists who rely on the generosity of brain donations. “If and when we go and look at something in human postmortem, we have to be very cautious about these technical issues.”

Llorens-Martin said she began carefully collecting and preserving brain samples in 2010, when she realized that many brains stored in brain banks were not adequately preserved for this kind of research. In their study, she and her colleagues examined the brains of people who died with their memories intact, and those who died at different stages of Alzheimer’s disease. She found that the brains of people with Alzheimer’s showed few if any signs of new neurons in the hippocampus—with less signal the further along the people were in the course of the disease. This suggests that the loss of new neurons—if it could be detected in the living brain—would be an early indicator of the onset of Alzheimer’s, and that promoting new neuronal growth could delay or prevent the disease that now affects more than 5.5 million Americans.

Rusty Gage, president of the Salk Institute for Biological Studies and a neuroscientist and professor there, says he was impressed by the researchers’ attention to detail. “Methodologically, it sets the bar for future studies,” says Gage, who was not involved in the new research but was the senior author in 1998 of a paper that found the first evidence for neurogenesis. Gage says this new study addresses the concerns raised by Alvarez-Buylla’s research. “From my view, this puts to rest that one blip that occurred,” he says. “This paper in a very nice way… systematically evaluates all the issues that we all feel are very important.”

Neurogenesis in the hippocampus matters, Gage says, because evidence in animals shows that it is essential for pattern separation, “allowing an animal to distinguish between two events that are closely associated with each other.” In people, Gage says, the inability to distinguish between two similar events could explain why patients with PTSD keep reliving the same experiences, even though their circumstances have changed. Also, many deficits seen in the early stages of cognitive decline are similar to those seen in animals whose neurogenesis has been halted, he says.

In healthy animals, neurogenesis promotes resilience in stressful situations, Gage says. Mood disorders, including depression, have also been linked to neurogenesis.

Hsieh says her research on epilepsy has found that newborn neurons get miswired, disrupting brain circuits and causing seizures and potential memory loss. In rodents with epilepsy, if researchers prevent the abnormal growth of new neurons, they prevent seizures, Hsieh says, giving her hope that something similar could someday help human patients. Epilepsy increases someone’s risk of Alzheimer’s as well as depression and anxiety, she says. “So, it’s all connected somehow. We believe that the new neurons play a vital role connecting all of these pieces,” Hsieh says.

In mice and rats, researchers can stimulate the growth of new neurons by getting the rodents to exercise more or by providing them with environments that are more cognitively or socially stimulating, Llorens-Martin says. “This could not be applied to advanced stages of Alzheimer’s disease. But if we could act at earlier stages where mobility is not yet compromised,” she says, “who knows, maybe we could slow down or prevent some of the loss of plasticity [in the brain].”


via
The Adult Brain Does Grow New Neurons After All, Study Says – Scientific American

, , ,

Leave a comment

[NEWS] Vitamin D Deficiency Linked to Loss in Brain Plasticity

Feb 21, 2019 | Original Press Release from the University of Queensland

Vitamin D Deficiency Linked to Loss in Brain Plasticity

Perineuronal nets (bright green) surround particular neurons (blue). Fluorescence labelling reveals just how detailed these structures are. Credit: Phoebe Mayne, UQ

University of Queensland research may explain why vitamin D is vital for brain health, and how deficiency leads to disorders including depression and schizophrenia.

 

via Vitamin D Deficiency Linked to Loss in Brain Plasticity | Technology Networks

, , , , , ,

Leave a comment

[News] Hope for epileptics as scientists discover device implanted in the brain cuts seizures by 93% – Daily Mail Online

  • Unnamed ‘chip’ gives out the proteins GDNFs in the hippocampus in the brain
  • GDNFs help produce dopamine, with low levels being associated with seizures
  • When implanted in epileptic rats, they were protected even once it was removed 

Scientists have raised hope for epileptics after creating a ‘chip’ that cuts seizures by 93 per cent over three months.

The device, which has not been named, continuously gives out the protein GDNF in an area of the brain known as the hippocampus, which is associated with epilepsy.

GDNF is critical to the production of the chemical messenger dopamine, with low levels being linked to seizures.

When the chip was implanted in the brains of epileptic rats, the rodents experienced 75 per cent fewer seizures after just two weeks.

And the animals continued to be protected even once the chip was removed, suggesting it modified the cells of the rodents’ brains, safeguarding them against epilepsy.

Scientists have raised hope for epileptics after creating a 'chip' that cuts seizures by 93 per cent over three months (stock image is a depiction of a patient after having a seizure)

Scientists have raised hope for epileptics after creating a ‘chip’ that cuts seizures by 93 per cent over three months (stock image is a depiction of a patient after having a seizure)

The research was carried out by the University of Ferrara, Italy, and Gloriana Therapeutics – the non-profit biotech company behind the chip.

It was led by Giovanna Paolone, a research assistant in the department of pharmacology at the university.

Around one in 100 people in the UK have epilepsy, which is defined as seizures that start in the brain, Epilepsy Society statistics reveal.

And in the US, 1.2 per cent of the population have the condition, according to the Centers for Disease Control and Prevention.

Targeting nerve tissue growth has been suggested as a way of treating epilepsy, however, getting the right concentration of drugs in the correct area of the brain has always been a challenge.

But scientists may have overcome this by developing a chip that continuously delivers GDNF (glial cell line-derived neurotrophic factor) where it needs to go. GDNF is expressed within the cells of the hippocampus.

The hippocampus – which stores memories – degrades following continued epileptics seizures, however, its exact role in the disease is unclear.

A third of patients with a form of epilepsy that affects the hippocampus are immune to treatment, which causes their condition to become more severe over time.


WHAT IS EPILEPSY?

Epilepsy is a condition that affects the brain and leaves patients at risk of seizures.

Around one in 100 people in the UK have epilepsy, Epilepsy Society statistics reveal.

And in the US, 1.2 per cent of the population have the condition, according to the Centers for Disease Control and Prevention.

Anyone can have a seizure, which does not automatically mean they have epilepsy.

Usually more than one episode is required before a diagnosis.

Seizures occur when there is a sudden burst of electrical activity in the brain, which causes a disruption to the way it works.

Some seizures cause people to remain alert and aware of their surroundings, while others make people lose consciousness.

Some also make patients experience unusual sensations, feelings or movement, or go stiff and fall to the floor where they jerk.

Epilepsy can be brought on at any age by a stroke, brain infection, head injury or problems at birth that lead to lack of oxygen.

But in more than half of cases, a cause is never found.

Anti-epileptic drugs do not cure the condition but help to stop or reduce seizures.

If these do not work, brain surgery can be effective.

Source: Epilepsy Action


The researchers genetically-modified cells found in the retina, known as ARPE-19, to produce high levels of GDNF before enclosing them in a semi-permeable membrane.  This allowed oxygen and nutrients in, while letting GDNF out.

To test the chip, scientists implanted it into the hippocampus of 37 rats. The rodents were made to be epileptic by injecting them with the drug pilocarpine, which is used to treat dry mouth and relieves pressure in the eyes.

Results revealed the chip reduced the number of motor seizures – when the muscles go stiff or weaken temporarily – by 75 per cent within two weeks and 93 per cent after three months.

The researchers then staggered the removal of the chips from rats by between one week and six months after they were implanted.

Even once the device was removed, the animals continued to experience less seizures, which suggests the device modified their disease.

They also showed decreased anxiety – a key complication of epilepsy. Anxiety was measured by the time the rats spent in the open area of a maze over ‘hiding’ in corners or close to the walls.

When the rats were put down and their brains examined, the scientists even found the chip reduced the degradation of their hippocampus.

Overall, the researchers claim their chip delivers GDNF in a ‘sustained, targeted, and efficacious manner’.

They hope the device will be tested in further animal studies and eventually in patients.

Ley Sander, medical director at Epilepsy Society and professor of neurology at University College London, told MailOnline: ‘Targeted treatments that go straight to the source of a seizure are offering real hope for the future in the treatment of epilepsy.

‘The hippocampus is a key area in the brain for generating seizures and for many with this type of epilepsy, their seizures are not controlled with conventional medications.

‘At Epilepsy Society our genomic research is trying to understand at an individual level what causes a person’s epilepsy. We believe this will enable us to deliver far more personalised medicines in the future.

‘Hopefully, the work of these scientists at the University of Ferrara in Italy may be a future option for some.’

via Hope for epileptics as scientists discover device implanted in the brain cuts seizures by 93% | Daily Mail Online

, , , , , , , ,

Leave a comment

[WEB SITE] A New Research for a better epilepsy treatment

A New Research for a better epilepsy treatment

About 1.2 percent of the population have active epilepsy. Although the majority of the people respond to anti-seizure medications, these medications may not work for every person. They may come with a risk of side effects. About 20 to 40 percent of patients with epilepsy continue to have seizures even after various anti-seizure medications.

Even when the drugs work, individuals may develop memory difficulties and depression. It may be due to the combination of the underlying seizure disorder and the drugs used to treat it.

A research team was led by Ashok K. Shetty. He is a Ph.D. professor at the Texas A&M College of Medicine. He is working on a permanent and better treatment for epilepsy. Their findings were published in the Proceedings of the National Academy of Sciences (PNAS).

“This publication by Dr. Shetty and his team is a step forward in treating incurable diseases of the brain,” said Darwin J. Prockop. He is an MD, Ph.D., the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine.

Working of excitatory and inhibitory neurons

Seizures are caused by the over-excitation of the excitatory neurons in the brain. Due to this overexcitation, they fire too much. And inhibitory neurons aren’t as abundant or aren’t effective at their optimum level.

Inhibitory neurons are required to stop the firing of excitatory neurons. Thus, the chief inhibitory neurotransmitter present in the brain is GABA, short for gamma-Aminobutyric acid.

Over the last decade, researchers have learned to generate induced pluripotent stem cells from normal adult cells, like a skin cell. Therefore, these stem cells can develop into nearly any type of cells in the body, including neurons which use GABA, called GABAergic interneurons.

“For this, transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy,” Shetty said.

The hippocampus is an area in the brain where seizures originate in temporal lobe epilepsy. It is also important for learning, mood, and memory. “Also, this region of brain functioned very well to overwhelm seizures. It even improves mental as well as mood functioning in the chronic epilepsy phase.”

Outcomes of the research

Additional testing exposed that the transplanted human neurons formed synapses with the excitatory neurons of the host. “They were also helpful for GABA and other markers of specific subclasses of inhibitory interneurons,” Shetty said.

“Another captivating aspect of this research is that transplanted human GABAergic neurons were found to be involved directly in controlling seizures. As silencing the transplanted GABAergic neurons caused an increased number of seizures.”

“One central aspect of the effort is that the similar cells can be attained from a patient.” This process, called autologous transplant, is patient specific. It means that there would be no rejection risk of the new neurons. And the person would not need anti-rejection drugs.

“However, we should make sure that we’re doing more good than harm,” Shetty said. “Going onward, we need to be certain that all the transplanted cells have turned into neurons. Because putting undifferentiated pluripotent stem cells could lead to tumors and other problems in the body.”

The epilepsy development often occurs after a head injury. That is why the Department of Defense is involved in funding the development of improved treatment and prevention options.

Treatment of other disorders

“Therefore, good research is essential before patients can be treated safely,” Prockop said. “But this study shows a technique through which patients can someday be treated with their own cells for the shocking epilepsy effects but possibly also other disorders like Parkinsonism and Alzheimer’s disease.”

Hence, Shetty advised that these tests were early interferences after the initial brain injury caused by status epilepticus. This is a state of continuous seizures in humans lasting more than five minutes.

The next phase is to understand if similar transplants would work for chronic epilepsy cases, mainly drug-resistant epilepsy. “Presently, there is no effective treatment for drug-resistant epilepsy. It is associated with memory problems, depression, and a death rate 5 to 10 times that of the general population,” he said.

“Hence, our findings propose that induced pluripotent stem cell-derived GABAergic cell therapy has the potential for providing a lifelong seizure control and releasing co-morbidities associated with epilepsy.”

 

via A New Research for a better epilepsy treatment

, , , , , , ,

Leave a comment

[TED Talk] The Brain-Changing Effects of Exercise

What’s the most transformative thing that you can do for your brain today? Exercise! says neuroscientist Wendy Suzuki. Get inspired to go to the gym as Suzuki discusses the science of how working out boosts your mood and memory — and protects your brain against neurodegenerative diseases like Alzheimer’s.

This talk was presented at an official TED conference, and was featured by our editors on the home page.

ABOUT THE SPEAKER
Wendy Suzuki · Neuroscientist, author Wendy Suzuki is researching the science behind the extraordinary, life-changing effects that physical activity can have on the most important organ in your body: your brain.

Transcript

03:54
05:02
07:13
09:41
11:13
12:12
12:43
12:46
12:47

via The Brain-Changing Effects of Exercise

, , , , , ,

Leave a comment

[WEB SITE] Neuroscientists unravel how two different types of brain plasticity work on synapses

 

The brain’s crucial function is to allow organisms to learn and adapt to their surroundings. It does this by literally changing the connections, or synapses, between neurons, strengthening meaningful patterns of neural activity in order to store information. The existence of this process – brain plasticity – has been known for some time.

But actually, there are two different types of brain plasticity at work on synapses. One is “Hebbian plasticity”; it is the one which effectively allows for the recording of information in the synapses, named after pioneering neuroscientist Donald Hebb. The other, more recently discovered, is “homeostatic synaptic plasticity” (HSP), and, like other “homeostatic” processes in the body such as maintaining a constant body temperature, its purpose is to keep things stable. In this case, HSP ensures that the brain doesn’t build up too much activity (as is the case in epilepsy) or become too quiet (as can happen when you lose synapses in Alzheimer’s Disease).

However, little is known about how these two types of plasticity actually interact in the brain. Now, a team of neuroscientists at the Champalimaud Centre for the Unknown, in Lisbon, Portugal, has begun to unravel the fundamental processes that happen in the synapse when the two mechanisms overlap. Their results were published in the journal iScience.

“In theory, the two types of plasticity act as opposing forces”, says Anna Hobbiss, first author of the new study, which was led by Inbal Israely. “Hebbian plasticity reacts to activity at the synapses by inciting them to get stronger while HSP reacts to it by making them weaker. We wanted to understand, on a cellular and molecular level, how the synapse deals with these two forces when they are present at the same time.”

In so doing, the authors have surprisingly shown that, contrary to what might be expected, HSP facilitates Hebbian plasticity, and thus influences memory formation and learning. This means that these two types of plasticity “may actually not be such distinct processes, but instead work together at the same synapses”, says Israely.

The team’s goal was to determine the changes in size of minute structures called dendritic spines, which are the “receiving end” of the synapse. The size of these spines changes to reflect the strength of the synaptic connection.

For this, they studied cells from the mouse hippocampus, a part of the brain which is crucial for learning. In their experiments, they blocked activity in the cells by introducing a potent neurotoxin called tetrodotoxin, thus simulating the loss of input to a certain part of the brain (“think about a person suddenly becoming blind, which leads to loss of input from the eyes to the brain”, says Hobbiss).

Forty eight hours later, they mimicked a small recovery of activity at only one synapse by releasing a few molecules of a neurotransmitter called glutamate on single spines of single neurons. This was possible thanks to a very high resolution, state-of-the-art laser technology, called two-photon microscopy, which allowed the scientists to very precisely visualize and target individual dendritic spines.

As this process evolved, the team closely watched what was happening to the spines – and they saw various anatomical changes. First, the silencing of all neural activity made the spines grow in size. “The spines are like little microphones, which, when there is silence, ramp up the ‘volume’ to try and catch even the faintest noise”, Hobbiss explains.

The scientists then activated individual spines with pulses of glutamate and watched them for two hours. One of the things they thought could happen was that the size of the spines would not grow further, since they had already turned up their ‘volume’ as far is it would go. But the opposite happened: the spines grew even more, with the smaller spines showing the biggest growth.

Finally, the authors also saw growth in neighboring spines, even though the experiment only targeted one spine. “We found that after a lack of activity, other spines in the vicinity also grew, further enhancing the cell’s sensitivity to restored neural transmission”, says Hobbiss. “The cells become more sensitive, more susceptible to encode information. It is as though the ‘gain’ has been turned up”, she adds.

“The fact that neighboring spines grew together with an active spine signifies that homeostatic plasticity changes one of the hallmark features of information storage, which is that plasticity is limited to the site of information entry”, Israely explains. “So, in this sense, the different plasticity mechanisms which are at work in the neuron can cooperate to change which and how many inputs respond to a stimulus. I think this is an exciting finding of our study.”

Taken together, these results show that homeostatic plasticity can actually rev up Hebbian plasticity, the type required for storing information. “Our work adds a piece to the puzzle of how the brain performs one of its fundamental tasks: being able to encode information while still keeping a stable level of activity”, concludes Hobbiss.

The misregulation of homeostatic plasticity – the stabilizing one – has started to be implicated in human health, specifically neurodevelopmental disorders such as Fragile X syndrome and Rett syndrome as well as neurodegenerative ones such as Alzheimer’s Disease. “Perhaps this balance is what allows us to be able to learn new information while retaining stability of that knowledge over a lifetime”, says Israely.

 

via Neuroscientists unravel how two different types of brain plasticity work on synapses

, , , , , , , , , , , ,

Leave a comment

[WEB PAGE] Study offers possibility of squelching a focal epilepsy seizure before symptoms appear

Patients with focal epilepsy that does not respond to medications badly need alternative treatments.

In a first-in-humans pilot study, researchers at the University of Alabama at Birmingham have identified a sentinel area of the brain that may give an early warning before clinical seizure manifestations appear. They have also validated an algorithm that can automatically detect that early warning.

These two findings offer the possibility of squelching a focal epilepsy seizure — before the patient feels any symptoms — through neurostimulation of the sentinel area of the brain. This is somewhat akin to the way an implantable defibrillator in the heart can staunch heart arrhythmias before they injure the heart.

In the pilot study, three epilepsy patients undergoing brain surgery to map the source of their focal epilepsy seizures also gave consent to add an investigational aspect to their planned surgeries.

As neurosurgeons inserted long, thin, needle-like electrodes into the brain to map the location of the electrical storm that initiates an epileptic seizure, they also carefully positioned the electrodes to add one more task — simultaneously record the electrical activity at the anterior nucleus of the thalamus.

The thalamus is a structure sitting deep in the brain that is well connected with other parts of the brain. The thalamus controls sleep and wakefulness, so it often is called the “pacemaker” of the brain. Importantly, preclinical studies have shown that focal sources of seizures in the cortex can recruit other parts of the brain to help generate a seizure. One of these recruited areas is the anterior thalamic nucleus.

The UAB team led by Sandipan Pati, M.D., assistant professor of neurology, found that nearly all of the epileptic seizures detected in the three patients — which began in focal areas of the cortex outside of the thalamus — also recruited seizure-like electrical activity in the anterior thalamic nucleus after a very short time lag. Importantly, both of these initial electrical activities appeared before any clinical manifestations of the seizures.

The UAB researchers also used electroencelphalography, or EEG, brain recordings from the patients to develop and validate an algorithm that was able to automatically detect initiation of that seizure-like electrical activity in the anterior thalamic nucleus.

“This exciting finding opens up an avenue to develop brain stimulation therapy that can alter activities in the cortex by stimulating the thalamus in response to a seizure,” Pati said. “Neurostimulation of the thalamus, instead of the cortex, would avoid interference with cognition, in particular, memory.”

“In epilepsy, different aspects of memory go down,” Pati explained. “Particularly long-term memory, like remembering names, or remembering events. The common cause is that epilepsy affects the hippocampus, the structure that is the brain’s memory box.”

Pati said these first three patients were a feasibility study, and none of the patients had complications from their surgeries. The UAB team is now extending the study to another dozen patients to confirm the findings.

“Hopefully, after the bigger group is done, we can consider stimulating the thalamus,” Pati said. That next step would have the goals of improved control of seizures and improved cognition, vigilance and memory for patients.

For epilepsy patients where medications have failed, the surgery to map the source of focal seizures is a prelude to two current treatment options — epilepsy surgery to remove part of the brain or continuous, deep-brain stimulation. If the UAB research is successful, deep brain stimulation would be given automatically, only as the seizure initiates, and it would be targeted at the thalamus, where the stimulation might interfere less with memory.

 

via Study offers possibility of squelching a focal epilepsy seizure before symptoms appear

, , , , , , , , , , , ,

Leave a comment

[BLOG POST] Do Older Brains Make New Neurons or Not?

Neurons in the brain. (Credit: Andrii Vodolazhskyi/Shutterstock)

Neurons in the brain. (Credit: Andrii Vodolazhskyi/Shutterstock)

One of the most basic things our bodies do is make new cells. It’s what allows tissues to grow and heal, and allows our bodies to continually rejuvenate themselves.

When it comes to cellular replenishment, one of the places researchers are most interested in is the brain. The formation of new brain cells is of critical interest to researchers studying everything from brain injuries to aging to mental illnesses like depression.

New Neurons Or No?

But researchers might be experiencing a bit of whiplash right now. Two papers, published just under a month apart, stand at odds with each other. One, led by researchers from the University of California, San Francisco, and published in Nature in early March, suggests that the hippocampus, a brain region important in the formation of memories, learning and emotional regulation, stops making new neurons after childhood, something that contradicts most previous research. The second, from Columbia University researchers out today in Cell Stem Cell, and using a very similar method, says that’s not true at all — the hippocampus does in fact make new cells throughout our lifespan.

It’s enough to tangle your neurons. But, it’s really a reminder that science is driven by debate and disagreement. It takes time and effort to arrive at a true consensus, and researchers can’t answer questions as definitively as we might wish.

In this case, the confusion seems to come down to methodology. Finding evidence of newly-formed neurons isn’t as simple as putting samples of brain tissue under a microscope. In fact, there are few direct ways of searching for neurogenesis. Instead, most researchers use indirect approaches, like searching for marker proteins involved in the maturation of new cells or other molecules somehow involved with cell development.

Though the way both teams of researchers looked for marker proteins differed slightly, both essentially involved highlighting cells expressing various marker proteins. They looked to see whether any cells “lit up”, and if so, checked to make sure they were actual new neurons.

What Do You See?

If both teams used the similar methods, how did they come to such different conclusions? Maura Boldrini, the author of the most recent paper who found the hippocampus continues to make new neurons throughout our lives, thinks it came down to the samples each team used.

“It’s not that they did something different from what we are doing substantially, I think it’s more a matter of what kind of tissue they had available,” she says. Boldrini studies how neurogenesis in the brain is related to things like depression and suicide. Over the years, she and others at Columbia University have built a large collection of brain tissue samples. Most importantly, she says, they had samples from people with healthy brains.

“As we started going on, we started having people with no psychiatric or neurological disease, no treatment, no history of drug abuse; spanning a big lifespan,” Boldrini says. “So we thought we had the right collection of brains to be able to look at the effects of aging, per se, without having these confounding factors … not too many brain collections in the world actually have information about this.”

The California researchers, says Sorrell, didn’t know the exact diagnosis of each brain sample, and had no toxicology reports for them. Drug use or psychological conditions like depression could affect the brain’s ability to make new neurons, potentially throwing the results off. In addition, some marker proteins begin to disappear soon after death, so if the samples aren’t preserved quickly, evidence of neurogenesis could be wiped away.

Another factor, Boldrini says, is the method of preservation. Some fixatives can obscure researchers’ ability to see certain types of cells. She encountered this problem during the course of her previous work, and that helped her choose the right fixatives to use. The California researchers used different fixatives than Boldrini did, and she thinks it’s another reason they might have come to different conclusions.

Counterpoint

Though Boldrini’s work agrees with the bulk of prior research into the subject, she and her team are still relying on an indirect method of imaging neurons, and it makes it difficult at the moment to close the book on the subject.

And not every researcher is convinced. Arturo Alvarez-Buylla is a neuroscientist at UC, San Francisco and a co-author of the paper that found no evidence of adult neurogenesis in the hippocampus. While he says more work needs to be done, he thinks Boldrini’s work may be misinterpreting some evidence, specifically the cells they label as new neurons.

“I believe what they are calling dividing cells and what they are calling new neurons, they may be [those things], but the evidence is not there,” Alvarez-Buylla says.

He points to a marker protein both his team and Boldrini’s use to search for developing cells, called Ki-67. Boldrini’s team likely misread figures showing the protein, Alvarez-Buylla thinks, leading them to falsely conclude that new neurons existed.

As for his own research, he says the fact they identified new neurons in samples of young tissue proves that his team’s methodology was solid, and that his results weren’t simply the result of poor sampling or fixing. They watched those cells dwindle and disappear as they looked at samples from progressively older people, which is evidence that neurogenesis does stop.

In fact, their method did turn up similar structures in adults as Boldrini did, Alvarez-Buylla says, but their interpretation differs.

“So, we did see the same cells that they do see in our post-mortem material, it’s just that we do not agree that they are young neurons,” he says.

Where Do We Stand?

Jonas Frisen, a stem cell researcher at Sweden’s Karolinska Institutet who was not involved with either study, agrees that the reason both teams got such different answers most likely lies in how they went about collecting and analyzing samples. Furthermore, drawing conclusions from negative data, as Alvarez-Buylla’s team did, is difficult.

“The commonly used quote, ‘Absence of evidence is not evidence of absence,’ summarizes that,” Frisen says in an email. “An analogy to the current situation is that you send 10 people into the woods to search for blueberries. Nine come back with blueberries and one not—are there blueberries in that forest?”

The method that both teams relied on has its drawbacks as well. There is a poor signal-to-noise ratio when searching for marker proteins in the brain, Frisen says, and much of the evidence that it works is based on animal studies — which may not fully translate to humans.

In the end, he agrees with Boldrini that humans probably continue to make neurons throughout the course of their lives. It would be good news for those of us worried about cracking our heads one too many times, though it obviously doesn’t change how our brains actually behave. The real benefit would be to researchers studying how the formation of new neurons relates to depression and other mental disorders, as well as how we make new memories and regulate emotions.

These past few weeks have been a case study in the machinations of science, and it serves as a solid reminder that there aren’t many hard-and-fast truths in science. And, new neurons or not, it’s another piece of the puzzle of how our brains work. In the end, that’s good for all of us.

via Do Older Brains Make New Neurons or Not?

, ,

Leave a comment

[WEB SITE] Researchers demonstrate synaptic plasticity in new-born neurons

Repeated stimulation enlarges dendritic spines

Even in adult brains, new neurons are generated throughout a lifetime. In a publication in the scientific journal PNAS, a research group led by Goethe University describes plastic changes of adult-born neurons in the hippocampus, a critical region for learning: frequent nerve signals enlarge the spines on neuronal dendrites, which in turn enables contact with the existing neural network.

Practice makes perfect, and constant repetition promotes the ability to remember. Researchers have been aware for some time that repeated electrical stimulation strengthens neuron connections (synapses) in the brain. It is similar to the way a frequently used trail gradually widens into a path. Conversely, if rarely used, synapses can also be removed – for example, when the vocabulary of a foreign language is forgotten after leaving school because it is no longer practiced. Researchers designate the ability to change interconnections permanently and as needed as the plasticity of the brain.

Plasticity is especially important in the hippocampus, a primary region associated with long-term memory, in which new neurons are formed throughout life. The research groups led by Dr Stephan Schwarzacher (Goethe University), Professor Peter Jedlicka (Goethe University and Justus Liebig University in Gieβen) and Dr Hermann Cuntz (FIAS, Frankfurt) therefore studied the long-term plasticity of synapses in new-born hippocampal granule cells. Synaptic interconnections between neurons are predominantly anchored on small thorny protrusions on the dendrites called spines. The dendrites of most neurons are covered with these spines, similar to the thorns on a rose stem.

In their recently published work, the scientists were able to demonstrate for the first time that synaptic plasticity in new-born neurons is connected to long-term structural changes in the dendritic spines: repeated electrical stimulation strengthens the synapses by enlarging their spines. A particularly surprising observation was that the overall size and number of spines did not change: when the stimulation strengthened a group of synapses, and their dendritic spines enlarged, a different group of synapses that were not being stimulated simultaneously became weaker and their dendritic spines shrank.

“This observation was only technically possible because our students Tassilo Jungenitz and Marcel Beining succeeded for the first time in examining plastic changes in stimulated and non-stimulated dendritic spines within individual new-born cells using 2-photon microscopy and viral labeling,” says Stephan Schwarzacher from the Institute for Anatomy at the University Hospital Frankfurt. Peter Jedlicka adds: “The enlargement of stimulated synapses and the shrinking of non-stimulated synapses was at equilibrium. Our computer models predict that this is important for maintaining neuron activity and ensuring their survival.”

The scientists now want to study the impenetrable, spiny forest of new-born neuron dendrites in detail. They hope to better understand how the equilibrated changes in dendritic spines and their synapses contribute the efficient storing of information and consequently to learning processes in the hippocampus.

 

via Researchers demonstrate synaptic plasticity in new-born neurons

, , , , , , , , ,

Leave a comment

[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

BY
LAUREL HAMERS, APRIL 5, 2018
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.
M. BOLDRINI/COLUMBIA UNIV.

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

, , , , , , ,

Leave a comment

%d bloggers like this: