Posts tagged science
Articles and news from the latest research reports.
University of Utah and German biologists discovered how nerve cells recycle tiny bubbles or “vesicles” that send chemical nerve signals from one cell to the next. The process is much faster and different than two previously proposed mechanisms for recycling the bubbles.
Researchers photographed mouse brain cells using an electron microscope after flash-freezing the cells in the act of firing nerve signals. That showed the tiny vesicles are recycled to form new bubbles only one-tenth of a second after they dump their cargo of neurotransmitters into the gap or “synapse” between two nerve cells or neurons.
“Without recycling these containers or ‘synaptic vesicles’ filled with neurotransmitters, you could move once and stop, think one thought and stop, take one step and stop, and speak one word and stop,” says University of Utah biologist Erik Jorgensen, senior author of the study in the Dec. 4 issue of the journal Nature.
“A fast nervous system allows you to think and move. Recycling synaptic vesicles allows your brain and muscles to keep working longer than a couple of seconds,” says Jorgensen, a distinguished professor of biology. “This process also may protect neurons from neurodegenerative diseases like Lou Gehrig’s disease and Alzheimer’s. So understanding the process may give us insights into treatments someday.”
A brain cell maintains a supply of 300 to 400 vesicles to send chemical nerve signals, using up to several hundred per second to release neurotransmitters, says the study’s first author, postdoctoral fellow Shigeki Watanabe.
Recycling vesicles is called “endocytosis.” Jorgensen and Watanabe named the process they observed “ultrafast endocytosis.” They showed it takes one-tenth of a second for a vesicle to be recycled, and such recycling occurs on the edge of “active zone” – the place on the end of the nerve cell where the vesicles first unload neurotransmitters into the synapse between brain cells.
“It’s like Whac-A-Mole: one vesicle goes down (fuses and unloads) and another pops up someplace else,” Jorgensen says.
Jorgensen believes ultrafast endocytosis is the most common way of recycling vesicles, but says the study doesn’t disprove two other, long-debated hypotheses:
– “Kiss-and-run endocytosis,” which supposedly takes one second, with a vesicle just “kissing” the inside of its nerve cell, dumping its neurotransmitters outside and “running” by detaching to reform a recycled vesicle in the same part of the active zone.
– Clathrin-mediated endocytosis,” which purportedly takes 20 seconds and occurs away from the active zone, at a point where a protein named clathrin assembles itself into a soccer-ball-shaped scaffold that forms a new vesicle or bubble.
Earlier this year, Jorgensen, Watanabe and colleagues published a related study in the journal eLife revealing that ultrafast endocytosis occurs in nematode worms. The new study of hippocampal brain cells from mice “tells us that mammals – and thus humans – do it the same way,” Jorgensen says. “The two papers together identify a process never previously seen – much faster than has been measured before.”
Jorgensen and Watanabe conducted the study with M. Wayne Davis, a University of Utah research assistant professor of biology; and technician Berit Söhl-Kielczynski and neuroscientists Christian Rosenmund, Benjamin Rost and Marcial Camacho-Pérez, all of Germany’s Charity University Medicine Berlin.
The study was funded by the National Institutes of Health, the European Research Council and the German Research Council. Jorgensen also is funded by his status as a Howard Hughes Medical Institute investigator and an Alexander von Humboldt Scholar.
Machine Gun Analogy for Vesicle Recycling
The process of a vesicle fusing to the nerve cell’s wall from the inside, then releasing neurotransmitters into the synapse is known as “exocytosis.” An analogy might be a bubble rising from boiling soup and releasing steam. The liquid part of the bubble fuses with the liquid in the soup, sooner or later to arise in another bubble.
The 2013 Nobel Prize in Physiology or Medicine went to three scientists who discovered key aspects of vesicle transport of cargo and exocytosis in nerve and other cells: which genes are required for vesicle transport, how vesicles deliver cargo to the correct locations, and how vesicles in brain cells release neurotransmitters to send a signal to the next brain neuron.
Jorgensen, Shigeki and colleagues studied the next step, endocytosis: how the membrane that forms vesicles (and nerve cell walls) is recycled to form new vesicles.
To illustrate the three possible mechanisms for recycling vesicles, Jorgensen compares vesicles with machine gun shells.
“You are fusing vesicles to the nerve cell membrane and expelling the neurotransmitter contents at extremely high rates,” he says. “The synapse will use up its ‘ammo’ very quickly at these rates, so the cell needs to refill the empty shells.”
Clathrin-mediated vesicle recycling is like “remaking the shell from scratch,” he says, while kiss-and-run endocytosis is like picking up every empty shell casing and refilling them one at a time.
“Ultrafast endocytosis allows the synapse to whip up all of the empty shells by the handful, fill them, and put them back in line at incredibly fast rates so the machine gun never runs out of ammo,” Jorgensen says.
Flash and Freeze for Nerve Cells in Action
Shigeki, Jorgensen and colleagues developed a method to photograph the tiny vesicles inside a nerve cell as the bubbles moved to the end of the cell, fused with the cell membrane, dumped their load of neurotransmitters into the gap or “synapse” between nerve cells, and then were recycled to reappear as new bubbles inside the nerve cell.
“We found a way to look at this process on a timescale that no one ever looked at before,” Watanabe says.
First, the researchers grew hundreds of brain cells from the mouse hippocampus – the often-studied part of the brain required for memory formation – on quarter-inch-wide sapphire disks placed in petri dishes with growth medium.
They added an algae gene to mouse brain cells that made the neurons produce an “ion channel” – basically a switch – that is stimulated by light instead of electricity. Then the brain cells were placed in a super-cold, high-pressure chamber, at 310 degrees below zero Fahrenheit and pressure 2,000 times greater than Earth’s atmosphere at sea level.
A wire cannot be routed into the chamber, which is why the cells were genetically programmed to be stimulated by light. The researchers flashed blue light on the mouse brain cells, making them “fire” neurotransmitter nerve signals. At the same time, the firing neurons were frozen with a blast of liquid nitrogen. To catch neurons in all stages of firing, the nerve cells were frozen at various times after the flash of blue light: 15, 30 and 100 milliseconds and one, three and 10 seconds.
“We built a new device to capture neurons performing fast behaviors,” Jorgensen says. “It stops all motion in the cell – even membranes in the act of fusing.
“We call it flash and freeze,” Watanabe says.
Next, the sapphire disks with neurons were put into liquid epoxy, which hardened and then were thin-sliced so the neurons could be photographed under an electron microscope. The ultrafast formation of recycled vesicles was visible.
“You see the outline of the membrane,” Jorgensen says. “You see the bubbles or vesicles in different stages of formation.”
Watanabe says about 3,000 mouse brain cell synapses were flashed, frozen and analyzed during the study. About 20 percent of the nerve cells had been fired and showed signs that nerve vesicles were being recycled.
Increased Brain Activity May Hold Key to Eliminating PTSD
In a new paper published in the current issue of Neuron, McLean Hospital and Harvard Medical School researchers report that increased activity in the medial prefrontal cortex (mPFC) of the brain is linked to decreased activity in the amygdala, the portion of the brain used in the creation of memories of events that scared those exposed.
According to author Vadim Bolshakov, PhD, director of the Cellular Neurobiology Laboratory at McLean and professor at Harvard Medical School, this finding is significant in that it could lead to better methods to prevent PTSD.
"A single exposure to something traumatic or scary can be enough to create a fear memory—causing someone to expect and be afraid in similar situations in the future," said Bolshakov. "What we’re seeing is that we may one day be able to prevent those fear memories."
Bolshakov and his colleagues tested their theory using animal models. Dividing the mice into two groups, some were taught to fear an auditory stimulus while in others fear memory was extinguished Increased activation of mPFC in extinguished animals led to inhibition of the amygdala and significant decreases in fear responses.
"For example, if a sound ended with an extremely loud shriek, a subject would come to expect that scary noise at the end of the sound," explained Bolshakov. "What we found was when we suppressed the fear memory by decreasing activity in the amygdala, the subjects were not afraid of the end of the auditory stimulus any longer."
Bolshakov notes that this work could have serious implications for the treatment of a number of conditions including PTSD.
"While there is still a great deal of research that needs to be done before our work can be translated to clinical trials, what we are showing has the potential to ensure that individuals exposed to trauma were not haunted by the conditions surrounding their initial stressor."
(Source: mclean.harvard.edu)
Missing “brake in the brain” can trigger anxiety states
Fear, at the right level, can increase alertness and protect against dangers. Disproportionate fear, on the other hand, can disrupt the sensory perception, be disabling, reduce happiness and therefore become a danger in itself. Anxiety disorders are therefore a psychiatric condition that should not be underestimated. In these disorders, the fear is so strong that there is tremendous psychological strain and living a normal life appears to be impossible. Researchers at the MedUni Vienna have now found a possible explanation as to how social phobias and fear can be triggered in the brain: a missing inhibitory connection or missing “brake” in the brain.
Inside the brain, the amygdala and the orbitofrontal cortex in the frontal lobe form an important control circuit for regulating the emotions. This control circuit is termed the brain’s emotional control centre. Whereas in healthy subjects, this circuit has “negative feedback” and “calmness” was identified, scientists used functional magnetic resonance imaging (MRI) on people with social phobias and found the opposite to be true: an important inhibitory connection is different in these patients, which may explain why they are unable to control their fears.
In collaboration with the Centre for Medical Physics and Biomedical Technology and the University Department of Psychiatry and Psychotherapy at the MedUni Vienna, the research team lead by Christian Windischberger was also able to discover through its recent study at the MedUni Vienna’s High Field MR Centre of Excellence how the areas of the brain that are involved with processing emotions are able to influence each other.
The study participants were shown a series of “emotional faces” while undergoing functional magnetic resonance imaging. fMRI is a non-invasive method which uses radio waves and magnetic fields to measure changes in the levels of oxygen in the blood and therefore neuronal activity in individual regions of the brain. An analysis method developed at University College London was used to provide new perspectives on the data obtained.
Breaking the circle of fear
When emotional facial expressions were shown - from laughing to crying, from happiness to anger - neuronal activity was triggered in the brain. The result: on a purely external basis, the test subjects looked no different, but the healthy subjects were kept calm thanks to their automatic “brake”, despite the emotional nature of the images. For the social phobics, on the other hand, the photographs put their brains into “overdrive”, triggering very strong neuronal activity. This was demonstrated very clearly using the new analysis method: “We have the opportunity not only to localise brain activity and compare it between groups, but we can now also make statements regarding functional connections within the brain. In psychiatric conditions especially, we can assume that there are not complete failures of these connections going on, but rather imbalances in complex regulatory processes,” says Ronald Sladky, the study’s primary author.
This better understanding of the neuronal mechanisms involved will now be used to develop new approaches to treatment. The aim is to understand what effect medications and psycho-therapeutic support have on the networks involved in order to help patients break out of their circles of fear.
(Source: meduniwien.ac.at)
Researchers Turn Current Sound-localization Theories ‘On their Ear’
The ability to localize the source of sound is important for navigating the world and for listening in noisy environments like restaurants, an action that is particularly difficult for elderly or hearing impaired people. Having two ears allows animals to localize the source of a sound. For example, barn owls can snatch their prey in complete darkness by relying on sound alone. It has been known for a long time that this ability depends on tiny differences in the sounds that arrive at each ear, including differences in the time of arrival: in humans, for example, sound will arrive at the ear closer to the source up to half a millisecond earlier than it arrives at the other ear. These differences are called interaural time differences. However, the way that the brain processes this information to figure out where the sound came from has been the source of much debate.
A recent paper by Mass. Eye and Ear/Harvard Medical School researchers in collaboration with researchers at the Ecole Normale Superieure, France, challenge the two dominant theories of how people localize sounds, explain why neuronal responses to sounds are so diverse and show how sound can be localized, even with the absence of one half of the brain. Their research is described on line in the journal eLife.
“Progress has been made in laboratory settings to understand how sound localization works, but in the real world people hear a wide range of sounds with background noise and reflections,” said Dan F. M. Goodman, lead author and post-doctoral fellow in the Eaton-Peabody Laboratories at Mass. Eye and Ear, Harvard Medical School. “Theories based on more realistic environments are important. The theme of the paper is that previous theories about this have been too idealized, and if you use more realistic data, you come to an entirely different conclusion.”
“Two theories have come to dominate our understanding of how the brain localizes sounds: the peak coding theory (which says that only the most strongly responding brain cells are needed), and the hemispheric coding theory (which says that only the average response of the cells in the two hemispheres of the brain are needed),” Goodman said. “What we’ve shown in this study is that neither of these theories can be right, and that the evidence they presented only works because their experiments used unnatural/idealized sounds. If you use more realistic, natural sounds, then they both do very badly at explaining the data.”
Researchers showed that to do well with realistic sounds, one needs to use the whole pattern of neural responses, not just the most strongly responding or average response. They showed two other key things: first, it has long been known that the responses of different auditory neurons are very diverse, but this diversity was not used in the hemispheric coding theory.
“We showed that the diversity is essential to the brain’s ability to localize sounds; if you make all the responses similar then there isn’t enough information, something that was not appreciated before because if one has unnatural/idealized sounds you don’t see the difference” Goodman said.
Second, previous theories are inconsistent with the well-known fact that people are still able to localize sounds if they lose one half of our brain, but only sounds on the other side (i.e. if one loses the left half of the brain, he or she can still localize sounds coming from the right), he added.
“We can explain why this is the case with our new theory,” Goodman said.
(Source: masseyeandear.org)
Prenatal Exposure to Alcohol Disrupts Brain Circuitry
Prenatal exposure to alcohol severely disrupts major features of brain development that potentially lead to increased anxiety and poor motor function, conditions typical in humans with Fetal Alcohol Spectrum Disorders (FASD), according to neuroscientists at the University of California, Riverside.
In a groundbreaking study, the UC Riverside team discovered that prenatal exposure to alcohol significantly altered the expression of genes and the development of a network of connections in the neocortex — the part of the brain responsible for high-level thought and cognition, vision, hearing, touch, balance, motor skills, language, and emotion — in a mouse model of FASD. Prenatal exposure caused wrong areas of the brain to be connected with each other, the researchers found.
These findings contradict the recently popular belief that consuming alcohol during pregnancy does no harm.
“If you consume alcohol when you are pregnant you can disrupt the development of your baby’s brain,” said Kelly Huffman, assistant professor of psychology at UC Riverside and lead author of the study that appears in the Nov. 27 issue of The Journal of Neuroscience, the official, peer-reviewed publication of the Society of Neuroscience. Study co-authors are UCR Ph.D. students Hani El Shawa and Charles Abbott.
“This research helps us understand how substances like alcohol impact brain development and change behavior,” Huffman explained. “It also shows how prenatal alcohol exposure generates dramatic change in the brain that leads to changes in behavior. Although this study uses a moderate- to high-dose model, others have shown that even small doses alter development of key receptors in the brain.”
Researchers have long known that ethanol exposure from a mother’s consumption of alcohol impacts brain and cognitive development in the child, but had not previously demonstrated a connection between that exposure and disruption of neural networks that potentially leads to changes in behavior.
Huffman’s team found dramatic changes in intraneocortical connections between the frontal, somatosensory and visual cortex in mice born to mothers who consumed ethanol during pregnancy. The changes were especially severe in the frontal cortex, which regulates motor skill learning, decision-making, planning, judgment, attention, risk-taking, executive function and sociality.
The neocortex region of the mammalian brain is similar in mice and humans, although human processing is more complex. In previous research, Huffman and her team created what amounts to an atlas of the neocortex, identifying the development of regions, gene expression and the cortical circuit over time. That research is foundational to understanding behavioral disorders such as autism and FASD.
Children diagnosed with FASD may have facial deformities and can exhibit cognitive, behavioral and motor deficits from ethanol-related neurobiological damage in early development. Those deficits may include learning disabilities, reduced intelligence, mental retardation and anxiety or depression, Huffman said.
Milder forms of FASD may produce no facial deformities, such as wideset eyes and smooth upper lip, but behavioral issues such as hyperactivity, hyperirritability and attention problems may appear as the child develops, she added.
Based on her earlier research, Huffman said, she expected to find some disruption of intraneocortical circuitry, but thought it would be subtle.
“I was surprised that the result of alcohol exposure was quite dramatic,” she said. “We found elevated levels of anxiety, disengaged behavior, and difficulty with fine motor coordination tasks. These are the kinds of things you see in children with FASD.”
The next phase of her research will examine whether deficits related to prenatal exposure to alcohol continue in subsequent generations.
The bottom line, Huffman said, is that women who are pregnant or who are trying to get pregnant should abstain from drinking alcohol.
“Would you put whiskey in your baby’s bottle? Drinking during pregnancy is not that much different,” she said. “If you ask me if you have three glasses of wine during pregnancy will your child have FASD, I would say probably not. If you ask if there will be changes in the brain, I would say, probably. There is no safe level of drinking during pregnancy.”
Molecular sensor detects early signs of multiple sclerosis
For some, the disease multiple sclerosis (MS) attacks its victims slowly and progressively over a period of many years. For others, it strikes without warning in fits and starts. But all patients share one thing in common: the disease had long been present in their nervous systems, hiding under the radar from even the most sophisticated detection methods. But now, scientists at the Gladstone Institutes have devised a new molecular sensor that can detect MS at its earliest stages—even before the onset of physical signs.
In a new study from the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, scientists reveal in animal models that the heightened activity of a protein called thrombin in the brain could serve as an early indicator of MS. By developing a fluorescently labeled probe specifically designed to track thrombin, the team found that active thrombin could be detected at the earliest phases of MS—and that this active thrombin correlates with disease severity. These findings, reported online in Annals of Neurology, could spur the development of a much-needed early-detection method for this devastating disease.
MS, which afflicts millions of people worldwide, develops when the body’s immune system attacks the protective myelin sheath that surrounds nerve cells. This attack damages the nerve cells, leading to a host of symptoms that include numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease’s underlying causes—causes that researchers are only just beginning to understand.
Last year, Dr. Akassoglou and her team found that a key step in the progression of MS is the disruption of the blood brain barrier (BBB). This barrier physically separates the brain from the blood circulation and if it breaks down, a blood protein called fibrinogen seeps into the brain. When this happens, thrombin responds by converting fibrinogen into fibrin—a protein that should normally not be present in the brain. As fibrin builds up in the brain, it triggers an immune response that leads to the degradation of the nerve cells’ myelin sheath, over time contributing to the progression of MS.
"We already knew that the buildup of fibrin appears early in the development of MS—both in animal models and in human patients, so we wondered whether thrombin activity could in turn serve as an early marker of disease." said Dr. Akassoglou, who directs the Gladstone Center for In Vivo Imaging Research (CIVIR). She is also a professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "In fact, we were able to detect thrombin activity even in our animal models—before they exhibited any of the disease’s neurological signs."
Alzheimer’s risk gene may begin to affect brains as early as childhood
People who carry a high-risk gene for Alzheimer’s disease show changes in their brains beginning in childhood, decades before the illness appears, new research from the Centre for Addiction and Mental Health (CAMH) suggests.
The gene, called SORL1, is one of a number of genes linked to an increased risk of late-onset Alzheimer’s disease, the most common form of the illness. SORL1 carries the gene code for the sortilin-like receptor, which is involved in recycling some molecules in the brain before they develop into beta-amyloid a toxic Alzheimer protein. SORL1 is also involved in lipid metabolism, putting it at the heart of the vascular risk pathway for Alzheimer’s disease as well.
“We need to understand where, when and how these Alzheimer’s risk genes affect the brain, by studying the biological pathways through which they work,” says Dr. Aristotle Voineskos, head of the Kimel Family Translational Imaging-Genetics Laboratory at CAMH, who led the study. “Through this knowledge, we can begin to design interventions at the right time, for the right people.” The study was recently published online in Molecular Psychiatry with Dr. Voineskos’s graduate student, Daniel Felsky as first author, and was a collaborative effort with the Zucker Hillside Hospital/Feinstein Institute in New York and the Rush Alzheimer’s Disease Center in Chicago.
To understand SORL1’s effects across the lifespan, the researchers studied individuals both with and without Alzheimer’s disease. Their approach was to identify genetic differences in SORL1, and see if there was a link to Alzheimer’s-related changes in the brain, using imaging as well as post-mortem tissue analysis.
In each approach, a link was confirmed.
In the first group of healthy individuals, aged eight to 86, researchers used a brain imaging technique called diffusion tensor imaging (DTI). Even among the youngest participants in the study, those with a specific copy of SORL1 showed a reduction in white matter connections in the brain important for memory performance and executive function.
The second sample included post-mortem brain tissue from 189 individuals less than a year old to 92 years, without Alzheimer’s disease. Among those with that same copy of the SORL1 gene, the brain tissue showed a disruption in the process by which the gene translated its code to become the sortilin-like receptor.
Finally, the third set of post-mortem brains came from 710 individuals, aged 66 to 108, of whom the majority had mild cognitive impairment or Alzheimer’s. In this case, the SORL1 risk gene was linked with the presence of amyloid-beta, a protein found in Alzheimer’s disease.
Dr. Voineskos notes that risk for Alzheimer’s disease results from a combination of factors – unhealthy diet, lack of exercise, smoking, high blood pressure combined with a person’s genetic profile – which all contribute to the development of the illness. “The gene has a relatively small effect, but the changes are reliable, and may represent one ‘hit’, among a pathway of hits required to develop Alzheimer’s disease later in life”.
While it’s too early to provide interventions that may target these changes, “individuals can take measures in their own lifestyle to reduce the risk of late-onset Alzheimer’s disease.” Determining whether there is an interaction with this risk gene and lifestyle factors will be one important next step.
In order to develop genetically-based interventions to prevent Alzheimer’s disease, the biological pathways of other risk genes also need to be systematically analyzed, the researchers note.
This research does, however, build on a previous CAMH imaging-genetics study on another gene related to Alzheimer’s disease. That study showed that a genetic variation of brain-derived neurotrophic factor (BDNF) affected brain structures in Alzheimer’s.
“The interesting connection is that BDNF may have important therapeutic value. But there is data to suggest that the effects of BDNF won’t work unless SORL1 is present, so there is the possibility that if you boost the activity of one gene, the other will increase,” says Dr. Voineskos, adding that BDNF therapeutics are in development. A next stage in the research, he says, is to look at the interaction of BDNF and SORL1.
(Source: camh.ca)
New compound for slowing the aging process can lead to novel treatments for brain diseases
A successful joint collaboration between researchers at the Hebrew university of Jerusalem and the startup company TyrNovo may lead to a potential treatment of brain diseases. The researchers found that TyrNovo’s novel and unique compound, named NT219, selectively inhibits the process of aging in order to protect the brain from neurodegenerative diseases, without affecting lifespan. This is a first and important step towards the development of future drugs for the treatment of various neurodegenerative maladies.
Human neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases share two key features: they stem from toxic protein aggregation and emerge late in life. The common temporal emergence pattern exhibited by these maladies proposes that the aging process negatively regulates protective mechanisms that prevent their manifestation early in life, exposing the elderly to disease. This idea has been the major focus of the work in the laboratory of Dr. Ehud Cohen of the Department of Biochemistry and Molecular Biology, at the Institute for Medical Research Israel-Canada in the Hebrew University of Jerusalem’s Faculty of Medicine.
Cohen’s first breakthrough in this area occurred when he discovered, working with worms, that reducing the activity of the signaling mechanism conveyed through insulin and the growth hormone IGF1, a major aging regulating pathway, constituted a defense against the aggregation of the Aβ protein which is mechanistically-linked with Alzheimer’s disease. Later, he found that the inhibition of this signaling route also protected Alzheimer’s-model mice from behavioral impairments and pathological phenomena typical to the disease. In these studies, the path was reduced through genetic manipulation, a method not applicable in humans.
Dr. Hadas Reuveni, the CEO of TyrNovo, a startup company formed for the clinical development of NT219, and Prof. Alexander Levitzki from the Department of Biological Chemistry at the Hebrew University, with their research teams, discovered a new set of compounds that inhibit the activity of the IGF1 signaling cascade in a unique and efficient mechanism, primarily for cancer treatment, and defined NT219 as the leading compound for further development.
Now, in a fruitful collaboration Dr. Cohen and Dr. Reuveni, together with Dr. Cohen’s associates Tayir El-Ami and Lorna Moll, have demonstrated that NT219 efficiently inhibits IGF1 signaling, in both worms and human cells. The inhibition of this signaling pathway by NT219 protected worms from toxic protein aggregation that in humans is associated with the development of Alzheimer’s or Huntington’s disease.
The discoveries achieved during this project, which was funded by the Rosetrees Trust of Britain, were published this week in the journal Aging Cell (“A novel inhibitor of the insulin/IGF signaling pathway protects from age-onset, neurodegeneration-linked proteotoxicity”). The findings strengthen the notion that the inhibition of the IGF1 signaling pathway has a therapeutic potential as a treatment for neurodegenerative disorders. They also point at NT219 as the first compound that provides protection from neurodegeneration-associated toxic protein aggregation through a selective manipulation of aging.
Cohen, Reuveni and Levitzki have filed a patent application that protects the use of NT219 as a treatment for neurodegenerative maladies through Yissum, the technology transfer company of the Hebrew University. Dr. Gil Pogozelich, chairman of Goldman Hirsh Partners Ltd., which holds the controlling interest in TyrNovo, says that he sees great importance in the cooperation on this project with the Hebrew University, and that TyrNovo represents a good example of how scientific and research initiatives can further health care together with economic benefits.
Recently, Dr. Cohen’s laboratory obtained an ethical approval to test the therapeutic efficiency of NT219 as a treatment in Alzheimer’s-model mice, hoping to develop a future treatment for hitherto incurable neurodegenerative disorders.
Novel Rehabilitation Device Improves Motor Skills after Stroke
Using a novel stroke rehabilitation device that converts an individual’s thoughts to electrical impulses to move upper extremities, stroke patients reported improvements in their motor function and ability to perform activities of daily living. Results of the study were presented today at the annual meeting of the Radiological Society of North America (RSNA).
"Each year, nearly 800,000 people suffer a new or recurrent stroke in the United States, and 50 percent of those have some degree of upper extremity disability," said Vivek Prabhakaran, M.D., Ph.D., director of functional neuroimaging in radiology at the University of Wisconsin-Madison. "Rehabilitation sessions with our device allow patients to achieve an additional level of recovery and a higher quality of life."
Dr. Prabhakaran, along with co-principal investigator Justin Williams, Ph.D., and a multidisciplinary team, built the new rehabilitation device by pairing a functional electrical stimulation (FES) system, which is currently used to help stroke patients recover limb function, and a brain control interface (BCI), which provides a direct communication pathway between the brain and this peripheral stimulation device.
In an FES system, electrical currents are used to activate nerves in paralyzed extremities. Using a computer and an electrode cap placed on the head, the new BCI-FES device (called the Closed-Loop Neural Activity-Triggered Stroke Rehabilitation Device) interprets electrical impulses from the brain and transmits the information to the FES.
"FES is a passive technique in that the electrical impulses move the patients’ extremities for them," Dr. Prabhakaran said. "When a patient using our device is asked to imagine or attempt to move his or her hand, the BCI translates that brain activity to a signal that triggers the FES. Our system adds an active component to the rehabilitation by linking brain activity to the peripheral stimulation device, which gives the patients direct control over their movement."
The Wisconsin team conducted a small clinical trial of their rehabilitation device, enlisting eight patients with one hand affected by stroke. The patients were also able to serve as a control group by using their normal, unaffected hand. Patients in the study represented a wide range of stroke severity and amount of time elapsed since the stroke occurred. Despite having received standard rehabilitative care, the patients had varying degrees of residual motor deficits in their upper extremities. Each underwent nine to 15 rehabilitation sessions of two to three hours with the new device over a period of three to six weeks.
The patients also underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) before, at the mid-point of, at the end of, and one month following the rehabilitation period. fMRI is able to show which areas of the brain are activated while the patient performs a task, and DTI reveals the integrity of fibers within the white matter that connects the brain’s functional areas.
Patients who suffered a stroke of moderate severity realized the greatest improvements to motor function following the rehabilitation sessions. Patients diagnosed with mild and severe strokes reported improved ability to complete activities of daily living following rehabilitation.
Dr. Prabhakaran said the results captured throughout the rehabilitation process—specifically the ratio of hemispheric involvement of motor areas—related well to the behavioral changes observed in patients. A comparison of pre-rehabilitation and post-rehabilitation fMRI results revealed reorganization in the regions of the brain responsible for motor function. DTI results over the course of the rehabilitation period revealed a gradual strengthening of the integrity of the fiber tracts.
"Our hope is that this device not only shortens rehabilitation time for stroke patients, but also that it brings a higher level of recovery than is achievable with the current standard of care," Dr. Prabhakaran said. "We believe brain imaging will be helpful in both planning and tracking a stroke patient’s therapy, as well as learning more about neuroplastic changes during recovery."
Study Suggests Low Vitamin D Causes Damage to Brain
A new study led by University of Kentucky researchers suggests that a diet low in vitamin D causes damage to the brain.
In addition to being essential for maintaining bone health, newer evidence shows that vitamin D serves important roles in other organs and tissue, including the brain. Published in Free Radical Biology and Medicine, the UK study showed that middle-aged rats that were fed a diet low in vitamin D for several months developed free radical damage to the brain, and many different brain proteins were damaged as identified by redox proteomics. These rats also showed a significant decrease in cognitive performance on tests of learning and memory.
"Given that vitamin D deficiency is especially widespread among the elderly, we investigated how during aging from middle-age to old-age how low vitamin D affected the oxidative status of the brain," said lead author on the paper Allan Butterfield, professor in the UK Department of Chemistry, director of the Center of Membrane Sciences, faculty of Sanders-Brown Center on Aging, and director of the Free Radical Biology in Cancer Core of the Markey Cancer Center. “Adequate vitamin D serum levels are necessary to prevent free radical damage in brain and subsequent deleterious consequences."
Previously, low levels of vitamin D have been associated with Alzheimer’s disease, and it’s also been linked to the development of certain cancers and heart disease. In both the developed world and in areas of economic hardship where food intake is not always the most nutritious, vitamin D levels in humans are often low, particularly in the elderly population. Butterfield recommends persons consult their physicians to have their vitamin D levels determined, and if low that they eat foods rich in vitamin D, take vitamin D supplements, and/or get at least 10-15 minutes of sun exposure each day to ensure that vitamin D levels are normalized and remain so to help protect the brain.
(Source: uknow.uky.edu)