#Genetics overlap found between Alzheimer's disease, cardiovascular risk factors The findings are published in current online issue of Circulation."
or skin cells or brain cells. We can use these new stem cells for future research to better understand how embryos are organized and
#Drugs stimulate body's own stem cells to replace the brain cells lost in multiple sclerosis Led by researchers at Case Western Reserve,
and human brain stem cells in the laboratory. The two most potent drugs--one that currently treats athlete's foot,
and the other, eczema--were capable of stimulating the regeneration of damaged brain cells and reversing paralysis
"We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis,
and results from aberrant immune cells destroying the protective coating, called myelin, around nerve cells in the brain and spinal cord.
Without myelin, neural signals cannot be transmitted properly along nerves; over time, a patient's ability to walk, hold a cup
Current multiple sclerosis therapies aim to slow further myelin destruction by the immune system, but the Case Western Reserve team used a new approach to create new myelin within the nervous system.
Their work offers great promise of developing therapies that reverse disabilities caused by multiple sclerosis or similar neurological disorders."
and less invasive approach by using drugs to activate native stem cells already in the adult nervous system
and direct them to form new myelin. Our ultimate goal was to enhance the body's ability to repair itself."
Specifically, the researchers developed a unique process to create massive quantities of a special type of stem cell called an oligodendrocyte progenitor cell (OPC.
These OPCS are normally found throughout the adult brain and spinal cord, and therefore inaccessible to study.
both drugs prompted native OPCS to regenerate new myelin.""It was a striking reversal of disease severity in the mice,
"said Robert Miller, Phd, a member of the neurosciences faculty at Case Western Reserve who,
"The drugs that we identified are able to enhance the regenerative capacity of stem cells in the adult nervous system.
a number of other disorders involve myelin loss or dysfunction including cerebral palsy, age-related dementia, optic neuritis and schizophrenia.
Any drugs developed that enhance myelination in multiple sclerosis also hold promise for benefiting these other disorders."
"The approach from Case Western Reserve University combines cutting-edge stem cell and drug screening technologies to develop new chemical therapeutics for myelin disorders,
and identify 5 specific receptors for dopamine and serotonin on their surface, two neurotransmitters that are essential to the body (see schema on page 2). The presence of these receptors on the surface of these stem cells indicated that they had the ability to respond to the presence of dopamine and serotonin in the event of a lesion.
The researchers naturally wondered what cells might be the source of these neurotransmitters a warning signal.
It turns out that the blood platelets, activated by the dental lesion, are responsible for releasing a large quantity of serotonin and dopamine.
Once released, these neurotransmitters then recruit the stem cells to repair the tooth by binding to their receptors (see schema on page 2). The research team was able to confirm this result by observing that dental repair was absent in rats with modified platelets that do not produce serotonin or dopamine,
i e. in the absence of the signal.""In stem cell research, it is unusual to be simultaneously able to isolate cell lines,
discover the signal that recruits them (serotonin and dopamine), and discover the source of that signal (blood platelets).
which the immune system attacks the protective myelin sheath, a type of insulation that covers nerves, ultimately disrupting communication between the brain and the body and leading to nerve deterioration.
To prevent neural degeneration requires remyelination through new oligodendrocytes, which create the myelin sheath. These two drugs, miconazole and clobetasol, were found to treat the source of the problem by reversing this process,
increasing the number of new oligodendrocytes and enhancing remyelination.""Current therapies focus on stopping immune system attacks,
slowing the progression of the disease. Our research is focused on trying to repair the brain itself,
to stop the disease rather than slow it, "said Robert Miller, Ph d.,co-author of the study and senior associate dean for research, Vivian Gill Distinguished Research Professor,
and professor of anatomy and regenerative biology at the George washington University School of medicine and Health Sciences."
researchers discovered the therapeutic compounds for enhancing myelination from oligodendrocyte progenitor cells through screening a library of bioactive small molecules.
Oligodendrocyte progenitor cells are stem cells found in the central nervous system and the principal source of myelinating oligodendrocytes.
and associate professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of medicine, found seven drugs that enhance generation of mature oligodendrocytes
and clobetasol could promote myelination. Miconazole was found to function directly as a remyelinating drug with no effect on the immune system,
and less invasive approach by using drugs to activate native stem cells already in the adult nervous system
and direct them to form new myelin. Our ultimate goal was to enhance the body's ability to repair itself.""
Their breakthrough, published in The Journal of Neuroscience, paves the way for a better understanding of chronic pain conditions.
"By studying mouse models, we first showed this gene is essential for the survival of neurons
and the development of the spinal cord,"explains Dr. Kania, Director of the Neural Circuit Development research unit at the IRCM."
"We then uncovered that removing the gene only in the spinal cord allows the mice to survive.
""We also discovered the missing gene leads to missing neurons, which, in turn, affects the proper development
and circuitry of the entire nervous system,"says Nora Szabo, Phd, postdoctoral fellow in Dr. Kania's laboratory and first author of the study."
"In fact, we observed a disruption in the connection between the spinal cord and specific brain centres,
""Our team was the first to study this gene specifically in the spinal cord, "adds Ronan V. da Silva,
""Seeing as little is known currently about the pain pathways in the nervous system, this breakthrough will help advance our understanding of pain sensation,"states Dr. Kania."
"The result of their efforts was 144 functional gene interaction networks for organs as diverse as the kidney, the liver and the whole brain.
"For example, with GIANT, researchers studying Parkinson's disease can search the substantia nigra network, which represents the brain region affected by Parkinson's,
to identify new genes and pathways involved in the disease.""Wong is one of three co-first authors of the paper.
#Switching on one-shot learning in the brain This type of one-shot learning is more than handy
Scientists have suspected long that one-shot learning involves a different brain system than gradual learning, but could not explain what triggers this rapid learning
or how the brain decides which mode to use at any one time. Now Caltech scientists have discovered that uncertainty in terms of the causal relationship
The researchers have identified also a part of the prefrontal cortex--the large brain area located immediately behind the forehead that is associated with complex cognitive activities--that appears to evaluate such causal uncertainty
a postdoctoral scholar in neuroscience at Caltech and lead author of the new paper.""If you are uncertain,
"The researchers used a simple behavioral task paired with brain imaging to determine where in the brain this causal processing takes place.
Based on the results, it appears that the ventrolateral prefrontal cortex (VLPFC) is involved in the processing and then couples with the hippocampus to switch on one-shot learning, as needed.
Indeed, a switch is an appropriate metaphor, says Shinsuke Shimojo, Caltech's Gertrude Baltimore Professor of Experimental psychology.
Since the hippocampus is known to be involved in so-called episodic memory, in which the brain quickly links a particular context with an event
the researchers hypothesized that this brain region might play a role in one-shot learning. But they were surprised to find that the coupling between the VLPFC
and the hippocampus was either all or nothing.""Like a light switch, one-shot learning is either on,
where their brains were monitored using functional Magnetic resonance imaging. The task consisted of multiple trials. During each trial, participants were shown a series of five images one at a time on a computer screen.
however, that they have not yet proven that the brain region actually controls the process in that way.
To prove that, they will need to conduct additional studies that will involve modifying the VLPFC's activity with brain stimulation
the researchers are intrigued by the fact that the VLPFC is very close to another part of the ventrolateral prefrontal cortex that they previously found to be involved in helping the brain to switch between two other forms of learning--habitual and goal-directed learning,
"Now we might cautiously speculate that a significant general function of the ventrolateral prefrontal cortex is to act as a leader,
telling other parts of the brain involved in different types of behavioral functions when they should get involved
The device is intended for use in remote laboratory settings to diagnose various types of cancers and nervous system disorders
#Cellular bubbles used to deliver Parkinson's meds directly to brain And what's the best way of getting her drug-packed exosomes to the brain?
It looks like a simple nasal spray will do the trick, say Elena Batrakova and her colleagues at the UNC Eshelman School of Pharmacy's Center for Nanotechnology in Drug Delivery.
and successfully loaded them with the enzyme catalase, a potent antioxidant that counters the neuron-killing inflammation responsible for Parkinson's and other degenerative neurological disorders.
This is the first time a large therapeutic protein like catalase has been delivered to the brain using exosomes. Getting drugs into the brain is extremely difficult in general
because it is protected and isolated from the rest of the body by the blood-brain barrier, which is extremely selective about
when a mind is changed Researchers studying how the brain makes decisions have recorded, for the first time the moment-by-moment fluctuations in brain signals that occur
when a monkey making free choices has a change of mind. The findings result from experiments led by electrical engineering Professor Krishna Shenoy,
whose Stanford lab focuses on movement control and neural prostheses--such as artificial arms--controlled by the user's brain."
"This basic neuroscience discovery will help create neural prostheses that can withhold moving a prosthetic arm until the user is certain of their decision,
They were performed by neuroscientist Matthew Kaufman while he was a graduate student in Shenoy's lab. Kaufman taught laboratory monkeys to perform a decision-making task.
He then developed a technique to track the brain signals that occur during a single decision with split-second accuracy.
"We are seeing many cognitive phenomena in the brain for the first time, "said Kaufman, who is now a postdoctoral scholar at Cold Spring Harbor Laboratory."
During the experiments, 192 electrodes in each monkey's motor and premotor cortex began measuring brain activity the moment that the targets appeared on screen.
Kaufman could analyze moment-by-moment brain activity during each individual decision. In a sense he was able to read the monkey's mind during free choices,
"We saw that the brain activity for a typical free choice looked just like it did forced for a choice.
"This deeper understanding of decision-making will help researchers to fine-tune the control algorithms of neural prostheses to enable people with paralysis to drive a brain-controlled prosthetic arm or guide a neurally-activated cursor on a computer screen.
In the early 1980s, University of California, San francisco neuroscientist Benjamin Libet conducted an experiment to assess the nature of free will.
Libet's experiments showed that distinctive brain activity began on average, several seconds before subjects became aware that they planned to move.
"Kaufman said that the brain activity Libet saw does not imply a demise of free will. Instead, his results show that you can plan to make a particular movement,
treatment with IVM can lead to brain or other neurologic damage that can be severe or fatal.
3-D printed'tissue'to help combat disease A bench-top brain that accurately reflects actual brain tissue would be significant for researching not only the effect of drugs,
and degenerative brain disease. Researchers have completed now 3-D printing a six-layered structure similar to brain tissue, in
which cells are placed accurately and remain in their designated layer. Researchers at the ARC Centre of Excellence for Electromaterials Science (ACES) have taken a step closer to meeting this challenge,
by developing a 3d printed layered structure incorporating neural cells, that mimics the structure of brain tissue.
The value of bench-top brain tissue is huge. Pharmaceutical companies spend millions of dollars testing therapeutic drugs on animals
but the human brain differs distinctly from that of an animal. A bench-top brain that accurately reflects actual brain tissue would be significant for researching not only the effect of drugs,
but brain disorders like schizophrenia, and degenerative brain disease. ACES Director and research author Professor Gordon Wallace said that the breakthrough is significant progress in the quest to create a bench-top brain that will enable important insights into brain function,
in addition to providing an experimental test bed for new drugs and electroceuticals.""We are still a long way from printing a brain
but the ability to arrange cells so as they form neuronal networks is a significant step forward,
"Professor Wallace said. To create their six-layered structure, researchers developed a custom bio-ink containing naturally occurring carbohydrate materials.
The result is layered a structure like brain tissue in which cells are placed accurately and remain in their designated layer."
a thin layer at the back of the eye that contains millions of nerve cells. Among those are called cells rods and cones,
which convert light into electrical impulses that are transmitted to vision centers in the brain. Loss of rods and cones is the primary cause of vision loss in diseases such as macular degeneration or retinitis pigmentosa.
But those diseases leave most remaining neurons within the retina relatively intact, and various technologies under development aim to restore vision by targeting the surviving cells.
However, following disruption of the circuit connecting the hippocampus and nucleus accumbens the rats became impatient and unwilling to wait, even for a few seconds.
Importantly, lesions to other parts of the brain, including the prefrontal cortex, known to be involved in certain aspects of decision-making,
and those with brain disease,"said Prof. Yogita Chudasama, of Mcgill's Psychology department and the lead researcher on the paper."
the hippocampus is thought to have a role in future planning, and the nucleus accumbens is a"reward"center and a major recipient of dopamine,
a chemical responsible for transmitting signals related to pleasure and reward, but we couldn't have imagined that the results would be so clear.
involving the hippocampus and nucleus accumbens, to be a therapeutic target in human patient groups
#Missing piece surfaces in the puzzle of autism A study carried out by the Laboratoire Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (CNRS/Aix-Marseille Université),
this complex condition evolves during brain development. The scientists thus chose to study adult olfactory stem cells as indicators of the early stages of ontogenesis
and can differentiate into neurons--constitute an interesting model to identify the genes and proteins whose expression is deregulated in patients with ASD.
so the scientists focused on the consequences of a deregulation of MOCOS synthesis. The analysis of different tissues demonstrated MOCOS expression in the brain cells and intestine of several species,
In these different organisms, under-expression of the enzyme induced hypersensitivity to oxidative stress (i e. to the toxicity of free radicals), a smaller number of synapses and abnormal neurotransmission due to a reduction in the number of vesicles carrying neurotransmitters.
--and its role in nerve development and neurotransmission mean it is an ideal candidate for deregulation of its expression to lead to the abnormal brain development observed in ASD.
and its regulators influence the development of the nervous system. This new study should help to shed light on how the brains of ASD patients establish abnormal connections,
while revealing new clinical and biological disturbances in these patients. This work therefore opens new pathways for research
#Super-small needle technology for the brain However, one challenge is reducing the tissue/neuron damage associated with needle penetration, particularly for chronic insert experiment and future medical applications.
However, such physically limited needles cannot penetrate the brain and other biological tissues because of needle buckling
and evaluated the penetration capability by using mouse brains in vitro/in vivo. In addition, as an actual needle application, we demonstrated fluorescenctce particle depth injection into the brain in vivo,
and confirm that by observing fluorescenctce confocal microscope"explained the first author, master's degree student Satoshi Yagi,
which allowed them to systematically test the response of individual neurons in the ant antennae to hydrocarbons found in the cuticles of worker ants and their queens.
After all, their incredible talent for olfactory discrimination depends not only on sensitively attuned neurons and an impressive collection of odorant receptors--ants have the largest odorant receptor gene family known in insects,
the leptin-in-antibody protein effectively could not cross from the bloodstream into the brain
#How traumatic memories hide in the brain, and how to retrieve them At first, hidden memories that can't be accessed consciously may protect the individual from the emotional pain of recalling the event.
when the brain is back in that state. In a new study with mice Northwestern Medicine scientists have discovered for the first time the mechanism by
The best way to access the memories in this system is to return the brain to the same state of consciousness as
Arrayarraytwo amino acids, glutamate and GABA, are the yin and yang of the brain, directing its emotional tides
and controlling whether nerve cells are excited or inhibited (calm). Under normal conditions the system is balanced. But when we are aroused hyper and vigilant, glutamate surges.
Glutamate is also the primary chemical that helps store memories in our neuronal networks in a way that they are easy to remember.
GABA, on the other hand, calms us and helps us sleep, blocking the action of the excitable glutamate.
benzodiazepine, activates GABA receptors in our brains. There are two kinds of GABA receptors. One kind, synaptic GABA receptors, works in tandem with glutamate receptors to balance the excitation of the brain in response to external events such as stress.
The other population extra-synaptic GABA receptors, are independent agents. They ignore the peppy glutamate.
Instead, their job is focused internally, adjusting brain waves and mental states according to the levels of internal chemicals, such as GABA, sex hormones and micro RNAS.
Extra-synaptic GABA receptors change the brain's state to make us aroused, sleepy, alert, sedated, inebriated or even psychotic.
However, Northwestern scientists discovered another critical role; these receptors also help encode memories of a fear-inducing event
and then store them away, hidden from consciousness.""The brain functions in different states, much like a radio operates at AM and FM frequency bands,
"Radulovic said.""It's as if the brain is tuned normally to FM stations to access memories,
but needs to be tuned to AM stations to access subconscious memories. If a traumatic event occurs
when these extra-synaptic GABA receptors are activated, the memory of this event cannot be accessed unless these receptors are activated once again,
essentially tuning the brain into the AM stations.""Arrayin the experiment, scientists infused the hippocampus of mice with gaboxadol,
a drug that stimulates extra-synaptic GABA receptors.""It's like we got them a little inebriated,
just enough to change their brain state, "Radulovic said. Then the mice were put in a box and given a brief, mild electric shock.
When the mice were returned to the same box the next day, they moved about freely and weren't afraid,
"This establishes when the mice were returned to the same brain state created by the drug,
when the extra-synaptic GABA receptors were activated with the drug, they changed the way the stressful event was encoded.
the brain used completely different molecular pathways and neuronal circuits to store the memory.""It's an entirely different system even at the genetic and molecular level than the one that encodes normal memories,
and may be the brain's protective mechanism when an experience is overwhelmingly stressful. The findings imply that in response to traumatic stress, some individuals,
activate the extra-synaptic GABA system and form inaccessible traumatic memories. Arraymemories are stored usually in distributed brain networks including the cortex
and can thus be accessed readily to consciously remember an event. But when the mice were in a different brain state induced by gaboxadol, the stressful event primarily activated subcortical memory regions of the brain.
The drug rerouted the processing of stress-related memories within the brain circuits so that they couldn't be accessed consciously d
#Major innovation in molecular imaging delivers spatial and spectral info simultaneously Ke Xu, a faculty scientist in Berkeley Lab's Life sciences Division, has dubbed his innovation SR-STORM,
Using this method to image neurons they showed that actin, a key component of the cytoskeleton (backbone of the cell), has a different structure in axons than in dendrites, two parts of a neuron.
But current super-resolution microscopy techniques do not deliver spectral information, which is useful for scientists to understand the behavior of individual molecules,
Alzheimer's, for example, may be related to degradation of the cytoskeleton inside neurons.""The cytoskeleton system is comprised of a host of interacting subcellular structures and proteins,
#Scientists discover atomic-resolution details of brain signaling"This is a very important, exciting advance that may open up possibilities for targeting new drugs to control neurotransmitter release.
Many mental disorders, including depression, schizophrenia and anxiety, affect neurotransmitter systems,"said Axel Brunger, the study's principal investigator.
He is a professor at Stanford School of medicine and SLAC and a Howard hughes medical institute investigator.""Both parts of this protein complex are said essential,
SNARES play a key role in the brain's chemical signaling by joining, or"fusing,"little packets of neurotransmitters to the outer edges of neurons,
where they are released and then dock with chemical receptors in another neuron to trigger a response.
Arrayin this latest research, the scientists found that when the SNARES and synaptotagmin-1 join up
triggering a gunshot-like release of neurotransmitters from one neuron to another. They also learned that the proteins join together before they arrive at a neuron's membrane,
which helps to explain how they trigger brain signaling so rapidly.""The neuron is not building the'gun'as it sits there on the membrane--it's already there,
"Brunger said. The team speculates that several of the joined protein complexes may group together
and simultaneously interact with the same vesicle to efficiently trigger neurotransmitter release, an exciting area for further studies."
"The structure of the SNARE-synaptotagmin-1 complex is a milestone that the field has awaited for a long time,
discovered synaptotagmin-1 and showed that it plays an important role as a calcium sensor and calcium-dependent trigger for neurotransmitter release."
who oversaw the development of the highly automated platform used for the neuroscience experiment, said,"This experiment was the first to use this robotic platform at LCLS to determine a previously unsolved structure of a large, challenging multi-protein complex."
Brunger said future studies will explore other protein interactions relevant to neurotransmitter release.""What we studied is only a subset,
#Scientists uncover nuclear process in the brain that may affect disease Every brain cell has a nucleus,
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte,
may play a critical role in health and disease. The study, published in the journal Nature Neuroscience, was funded partially by the National institutes of health (NIH."
"Unexpectedly we may have discovered a hidden pathway to understanding how astrocytes respond to injury and control brain processes.
The pathway may be common to many brain diseases and we're just starting to follow it,
"said Katerina Akassoglou, Ph d.,a senior investigator at the Gladstone Institute for Neurological disease, a professor of neurology at the University of California, San francisco,
Some neurological disorders are associated with higher than normal brain levels of the growth factor TGF-beta,
astrocytes produce greater amounts of p75 neurotrophin receptor (p75ntr), a protein that helps cells detect growth factors.
Dr. Akassoglou's lab showed that eliminating the p75ntr gene prevented hydrocephalus in mice genetically engineered to have astrocytes that produce higher levels of TGF-beta.
Hydrocephalus is a disorder that fills the brain with excess cerebral spinal fluid. Eliminating the p75ntr gene also prevented astrocytes in the brains of the mice from forming scars after injuries and restored gamma oscillations
which are patterns of neuronal activity associated with learning and memory. The cell nucleus is a ball of chromosomes wrapped in a protective fatty membrane.
In this study, the researchers discovered that treating astrocytes with TGF-beta freed a small piece of the p75ntr protein to bind to nucleoporins,
and enables astrocytes to enter a reactive state.""This research highlights the importance of the nuclear pore complex in the brain
and raises the possibility that it may be a target for treating a wide range of neurological disorders,
The scientists used high-resolution microscopes to watch the astrocyte nucleus in action. Nuclear pores that did not have the p75ntr gene were slightly larger than normal.
When the scientists treated astrocytes with TGF-beta, they saw p75ntr proteins bind to nucleoporins
which is essential for TGF-beta to exert its effects on astrocytes. In other experiments, the scientists showed that eliminating p75ntr from astrocytes blocked the transport of Smad2 into the nucleus."Nuclear pores are gatekeepers
and p75ntr appears to be the key to unlocking particular gates,""said Dr. Akassoglou.""We discovered novel roles for both players
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