Posts tagged nerve cells
Articles and news from the latest research reports.
Genes for autism and schizophrenia only active in developing brains
Genes linked to autism and schizophrenia are only switched on during the early stages of brain development, according to a collaboration between researchers at Imperial College London, the University of Oxford and King’s College London.
This new study adds to the evidence that autism and schizophrenia are neurodevelopmental disorders, a term describing conditions that originate during early brain development.
The researchers studied gene expression in the brains of mice throughout their development, from 15-day old embryos to adults, and their results are published in Proceedings of the National Academy of Sciences.
The research focused on cells in the ‘subplate’, a region of the brain where the first neurons (nerve cells) develop. Subplate neurons are essential to brain development, and provide the earliest connections within the brain.
'The subplate provides the scaffolding required for a brain to grow, so is important to consider when studying brain development,' says Professor Zoltán Molnár, senior author of the paper from the University of Oxford, 'Looking at the pyramids in Egypt today doesn't tell us how they were actually built. Studying adult brains is like looking at the pyramids today, but by studying the developing brains we are able to see the transient scaffolding that has been used to construct it.'
The study shows that certain genes linked to autism and schizophrenia are only active in the subplate during specific stages of development. The data analysis was designed by Dr Enrico Petretto, Senior Lecturer in Genomic Medicine at Imperial College London. Dr Petretto said: “We looked at the full network of genes in the brain to identify which pathways play a role in early brain development. This allowed us to find coherent clusters of genes previously associated with susceptibility to autism spectrum disorders or schizophrenia. These results provide a unique resource for our understanding of how gene behaviour changes in the mouse subplate from the early embryonic stage to adulthood. This means we are better equipped to investigate how the gene network changes in the developing brain and identify any links with neurodevelopmental disorders.”
The team was able to map gene activity in full detail thanks to these new methods which allowed them to dissect and profile gene expression from small numbers of cells. This also enabled them to identify the different populations of subplate neurons more accurately.
Professor Hugh Perry, chair of the Medical Research Council’s Neuroscience and Mental Health Board, said: “By being able to pinpoint common genetic factors for neurological conditions such as autism and schizophrenia, scientists are able to understand an important part of the story as to why things go awry as our brains develop. The Medical Research Council’s commitment to a broad portfolio of neuroscience and mental health research places us in a unique position to respond to the challenge of mental ill health and its relationship with physical health and wellbeing.”
(Source: www3.imperial.ac.uk)
Gene gives motor neurone disease insight
A discovery using stem cells from a patient with motor neurone disease could help research into treatments for the condition.
The study used a patient’s skin cells to create motor neurons - nerve cells that control muscle activity - and the cells that support them called astrocytes.
Astrocyte death
Researchers studied these two types of cells in the laboratory. They found that a protein expressed by abnormalities in a gene linked to motor neurone disease, which is called TDP-43, caused the astrocytes to die.
The study, led by the University of Edinburgh and funded by the Motor Neurone Disease Association, provides fresh insight into the mechanisms involved in the disease.
Gene mutation
Although TDP-43 mutations are a rare cause of motor neurone disease (MND), scientists are especially interested in the gene because in the vast majority of MND patients, TDP-43 protein (made by the TDP-43 gene) forms pathological clumps inside motor neurons.
Motor neurones die in MND leading to paralysis and early death.
This study shows for the first time that abnormal TDP-43 protein causes death of astrocytes.
The researchers, however, found that the damaged astrocytes were not directly toxic to motor neurons.
Motor neurone disease is a devastating and ultimately fatal condition, for which there is no cure or effective treatment. -Professor Siddharthan Chandran (Director of the Euan Macdonald Centre for Motor Neurone Disease Research)
Implications
Better understanding the role of astrocytes could help to inform research into treatments for motor neurone disease (MND).
These findings, published in the journal Proceedings of the National Academy of Sciences, are significant as they show that different mechanisms are at work in different types of MND.
It is not just a question of looking solely at motor neurons, but also the cells that surround them, to understand why motor neurones die. Our aim is to find ways to slow down progression of this devastating disease and ultimately develop a cure. -Professor Siddharthan Chandran (Director of the Euan Macdonald Centre for Motor Neurone Disease Research)
(Source: ed.ac.uk)
Finding challenges accepted view of MS: Unexpectedly, damaged nerve fibers survive
Multiple sclerosis, a brain disease that affects over 400,000 Americans, causes movement difficulties and many neurologic symptoms. MS has two key elements: The nerves that direct muscular movement lose their electrical insulation (the myelin sheath) and cannot transmit signals as effectively. And many of the long nerve fibers, called axons, degenerate.
Many scientists believe that axons are doomed once they lose the insulation, but a new study by graduate student Chelsey Smith and former undergraduate Elizabeth Cooksey in the Journal of Neuroscience shows axons can survive for long periods in rats even after losing myelin.
"This was the first study to demonstrate long-term axon survival after myelin deterioration," says senior author Ian Duncan, a professor in the School of Veterinary Medicine at the University of Wisconsin-Madison.
The mutant rats in the experiment have substantial myelin at first, but by eight weeks the essential myelin insulation is lost. “It was surprising,” says Duncan, an expert in MS pathology. “Nine months is a relatively long period in a rat’s lifetime, and there wasn’t a loss of axons, so the assumption that axons must automatically die without myelin seems incorrect.”
Green tea and red wine extracts interrupt Alzheimer’s disease pathway in cells
Natural chemicals found in green tea and red wine may disrupt a key step of the Alzheimer’s disease pathway, according to new research from the University of Leeds.
In early-stage laboratory experiments, the researchers identified the process which allows harmful clumps of protein to latch on to brain cells, causing them to die. They were able to interrupt this pathway using the purified extracts of EGCG from green tea and resveratrol from red wine.
The findings, published in the Journal of Biological Chemistry, offer potential new targets for developing drugs to treat Alzheimer’s disease, which affects some 800,000 people in the UK alone, and for which there is currently no cure.
"This is an important step in increasing our understanding of the cause and progression of Alzheimer’s disease," says lead researcher Professor Nigel Hooper of the University’s Faculty of Biological Sciences. "It’s a misconception that Alzheimer’s is a natural part of ageing; it’s a disease that we believe can ultimately be cured through finding new opportunities for drug targets like this."
Alzheimer’s disease is characterised by a distinct build-up of amyloid protein in the brain, which clumps together to form toxic, sticky balls of varying shapes. These amyloid balls latch on to the surface of nerve cells in the brain by attaching to proteins on the cell surface called prions, causing the nerve cells to malfunction and eventually die.
"We wanted to investigate whether the precise shape of the amyloid balls is essential for them to attach to the prion receptors, like the way a baseball fits snugly into its glove," says co-author Dr Jo Rushworth. "And if so, we wanted to see if we could prevent the amyloid balls binding to prion by altering their shape, as this would stop the cells from dying."
The team formed amyloid balls in a test tube and added them to human and animal brain cells. Professor Hooper said: “When we added the extracts from red wine and green tea, which recent research has shown to re-shape amyloid proteins, the amyloid balls no longer harmed the nerve cells. We saw that this was because their shape was distorted, so they could no longer bind to prion and disrupt cell function.
"We also showed, for the first time, that when amyloid balls stick to prion, it triggers the production of even more amyloid, in a deadly vicious cycle," he added.
Professor Hooper says that the team’s next steps are to understand exactly how the amyloid-prion interaction kills off neurons.
"I’m certain that this will increase our understanding of Alzheimer’s disease even further, with the potential to reveal yet more drug targets," he said.
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, which part-funded the study, said: “Understanding the causes of Alzheimer’s is vital if we are to find a way of stopping the disease in its tracks. While these early-stage results should not be a signal for people to stock up on green tea and red wine, they could provide an important new lead in the search for new and effective treatments. With half a million people affected by Alzheimer’s in the UK, we urgently need treatments that can halt the disease – that means it’s crucial to invest in research to take results like these from the lab bench to the clinic.”
Reflex control could improve walking after incomplete spinal injuries
A training regimen to adjust the body’s motor reflexes may help improve mobility for some people with incomplete spinal cord injuries, according to a study supported by the National Institutes of Health.
During training, the participants were instructed to suppress a knee jerk-like reflex elicited by a small shock to the leg. Those who were able to calm hyperactive reflexes – a common effect of spinal cord injuries – saw improvements in their walking.
The study was led by Aiko Thompson, Ph.D., and Jonathan Wolpaw, M.D., both of whom hold appointments at the New York state Department of Health and the State University of New York in Albany, and at Columbia University in New York City. The study took place at Helen Hayes Hospital in West Haverstraw, N. Y. It was funded in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS), and published in the Journal of Neuroscience.
"People tend to think of reflexes as fixed, but in reality, normal movement requires constant fine tuning of reflexes by the brain. Loss of that fine-tuning is an important part of the disability that comes with a spinal cord injury," said Dr. Wolpaw, a research physician and professor at the Wadsworth Center, the state health department’s public health laboratory.
When the brain makes a decision to move, it sends signals that travel through the spinal cord to the appropriate muscles. Spinal reflexes – controlled by local circuits of nerve cells in the spinal cord – provide a way for the body to react and move quickly without a conscious decision from the brain. “They enable you to jerk your hand away from a hot stove before you’ve registered the pain and experienced severe burns,” Dr. Wolpaw said. “The brain can gradually enhance or suppress reflexes as needed,” he said.
Stroke Damage in Mice Overcome by Training that ‘Rewires’ Brain Centers
Johns Hopkins researchers have found that mice can recover from physically debilitating strokes that damage the primary motor cortex, the region of the brain that controls most movement in the body, if the rodents are quickly subjected to physical conditioning that rapidly “rewires” a different part of the brain to take over lost function.
Their research, featuring precise, intense and early treatment, and tantalizing clues to the role of a specific brain area in stroke recovery, is described online in the journal Stroke.
"Despite all of our approved therapies, stroke patients still have a high likelihood of ending up with deficits," says study leader Steven R. Zeiler, M.D., Ph.D., an assistant professor of neurology at the Johns Hopkins University School of Medicine. "This research allows us the opportunity to test meaningful training and pharmacological ways to encourage recovery of function, and should impact the care of patients."
With improved acute care for stroke, more patients are surviving. Still, as many as 60 percent are left with diminished use of an arm or leg, and one-third need placement in a long-term care facility. The economic cost of disability translates to more than $30 billion in annual care.
Our ability to learn and form new memories is fully dependent on the brain’s ability to be plastic – that is to change and adapt according to new experiences and environments. A new study from the Montreal Neurological Institute – The Neuro, McGill University, reveals that DCC, the receptor for a crucial protein in the nervous system known as netrin, plays a key role in regulating the plasticity of nerve cell connections in the brain. The absence of DCC leads to the type of memory loss experienced by Dr. Brenda Milner’s famous subject HM. Although HM’s memory loss resulted from the removal of an entire brain structure, this study shows that just removing DCC causes the same type of memory deficit. The finding published in this week’s issue of Cell Reports, extends Dr. Milner’s seminal finding to another level, revealing a key part of the molecular basis for learning and memory.
Although both netrin and DCC are essential for normal development (in terms of guiding nerve cell growth) until now their function in the adult brain was not known. Dr. Tim Kennedy, lead researcher and neuroscientist at The Neuro, contributed to the discovery of netrins as a young post-doctoral fellow. This new study reveals the answer to the question that drove him to first start a lab. “I remember that exact moment when I knew I could run a research lab, it was 1993 and I was studying the developing nervous system and I was amazed to spot netrins in the adult brain - raising the important question, ‘what are they doing there?’ 20 years of dedicated research later the answer provides an important piece of the puzzle for understanding our nervous system and neurological disorders.
“The power of this study is that it looks at the animal on all levels, molecular, structural, and behavioural. We show that the netrin receptor DCC is a critical component of synapses between neurons in the adult brain, and is required for synapses to function properly. To demonstrate this, we selectively removed DCC from a specific subset of neurons in the adult mouse brain. This results in progressive degeneration of synapses, leading to defects in synaptic plasticity and memory. The synapses continue to function in that they still communicate but, the synapses cannot adjust or change in response to new experiences. Therefore, you can’t learn anymore.”
Furthermore, DCC deletion from mature neurons results in changes in the shape of specialized protrusions called dendritic spines, and alters the NMDA receptor, a critical trigger for mechanisms that make changes in synaptic strength. Therefore the study reveals that DCC is required to maintain proper synapse morphology or shape, and to regulate the ability of the NMDA receptor to switch on, which ensures activity-dependent synaptic plasticity.
Chemical reaction keeps stroke-damaged brain from repairing itself
Nitric oxide, a gaseous molecule produced in the brain, can damage neurons. When the brain produces too much nitric oxide, it contributes to the severity and progression of stroke and neurodegenerative diseases such as Alzheimer’s. Researchers at Sanford-Burnham Medical Research Institute recently discovered that nitric oxide not only damages neurons, it also shuts down the brain’s repair mechanisms. Their study was published by the Proceedings of the National Academy of Sciences the week of February 4.
“In this study, we’ve uncovered new clues as to how natural chemical reactions in the brain can contribute to brain damage—loss of memory and cognitive function—in a number of diseases,” said Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.
Lipton led the study, along with Sanford-Burnham’s Tomohiro Nakamura, Ph.D., who added that these new molecular clues are important because “we might be able to develop a new strategy for treating stroke and other disorders if we can find a way to reverse nitric oxide’s effect on a particular enzyme in nerve cells.”
Nitric oxide inhibits the neuroprotective ERK1/2 signaling pathway
Learning and memory are in part controlled by NMDA-type glutamate receptors in the brain. These receptors are linked to pores in the nerve cell membrane that regulate the flow of calcium and sodium in and out of the nerve cells. When these NMDA receptors get over-activated, they trigger the production of nitric oxide. In turn, nitric oxide attaches to other proteins via a reaction called S-nitrosylation, which was first discovered by Lipton and colleagues. When those S-nitrosylated proteins are involved in cell survival and lifespan, nitric oxide can cause brain cells to die prematurely—a hallmark of neurodegenerative disease.
In their latest study, Lipton, Nakamura and colleagues used cultured neurons as well as a living mouse model of stroke to explore nitric oxide’s relationship with proteins that help repair neuronal damage. They found that nitric oxide reacts with the enzyme SHP-2 to inhibit a protective cascade of molecular events known as the ERK1/2 signaling pathway. Thus, nitric oxide not only damages neurons, it also blocks the brain’s ability to self-repair.
Molecule key to sustaining brain communication
Scientists have discovered the powerful role the molecule Myosin VI plays in communication between nerve cells in the brain.
Researchers at the University of Queensland’s (UQ) Queensland Brain Institute (QBI) have found that Myosin VI is integral to maintaining the neurotransmitter release that allows neurons to pass on information to other neurons.
The discovery made by Vanesa Tomatis, a PhD student in Associate Professor Frederic Meunier’s laboratory, demonstrates how Myosin VI has the impressive ability to anchor secretory vesicles that are at least 5,000 times greater in size, near their release site.
"By tethering and anchoring secretory granules, Myosin VI helps to maintain an active pool of vesicles near the plasma membrane, which is key to sustaining communication between neuronal cells," Associate Professor Meunier said.
Associate Professor Meunier and his team are now looking to better understand how the Myosin VI manages to grab and hold vesicles through the use of super resolution microscopy.
They hope the discovery will lead to new ways to reinstate or regulate neuronal communication in various brain disorders.
The paper was published in The Journal of Cell Biology on February 4 2013
(Image credit: Wikipedia)
New drug target identified for multiple sclerosis and Alzheimer’s disease
Researchers at Boston University School of Medicine (BUSM) led by Carmela Abraham, PhD, professor of biochemistry, along with Cidi Chen, PhD, and other collaborators, report that the protein Klotho plays an important role in the health of myelin, the insulating material allowing for the rapid communication between nerve cells. These findings, which appear online in Journal of Neuroscience, may lead to new therapies for multiple sclerosis (MS) and Alzheimer’s disease (AD), in which white matter abnormalities are also common but have been largely ignored.
MS is an inflammatory disease which damages the fatty myelin sheaths around the axons of the brain and spinal cord. This destruction, loss or scarring of the sheaths results in a broad spectrum of symptoms. Disease onset usually occurs in young adults, most commonly women.
In MS the myelin is attacked by the immune system and may not be completely restored by myelin-producing cells (mature oligodendrocytes). The researchers discovered that the addition of Klotho protein to immature oligodendrocytes causes them to mature and manufacture proteins needed for the production of healthy myelin.
"These results taken together indicate that Klotho could become a drug target for multiple sclerosis and other white matter diseases, including AD," explained Abraham.
Abraham and her colleagues have identified, and are working on optimizing, a number of small molecules that could form the basis for the development of therapeutic drugs, which would increase the amount of Klotho protein in the brain.
Since Klotho is not only an age suppressor but also a tumor suppressor, as shown by other research groups, interventions with Klotho-enhancing drugs may solve some of the most treatment-resistant human ailments according to Abraham.
Klotho was named after the Greek Goddess and daughter of Zeus, who spins the thread of life. Abraham’s lab was the first to publish (in 2008) that Klotho levels in the brain decrease with age.
(Source)