Neuroscience

Cigarettes have already been linked to a plethora of different diseases and adverse health conditions, and now a new study has found that the smoking could also increase the risk of developing cataracts in some individuals.

Dr. Juan Ye of the Zhejiang University Institute of Ophthalmology and colleagues conducted a meta-analysis, reviewing a dozen cohorts and eight case-control studies from five continents (Africa, Asia, Australia, Europe and North America) to determine smoking’s impact on the development of age-related cataracts, the leading cause of vision loss and blindness in the world.

They looked at the occurrence of age-related cataract in individuals who had smoked cigarettes versus those who had never lit up. They also looked at the differences between former and current smokers, as well as each of the three different types of cataract that can develop in older individuals, the Association for Research and Vision in Ophthalmology (ARVO) explained in an October 12 press release.

“The results showed that every individual that ever smoked cigarettes was associated with an increased risk of age-related cataract, with a higher risk of incidence in current smokers,” they said, adding that “former and current smokers showed a positive association with two of the subtypes: nuclear cataract, when the clouding is in the central nucleus of the eye, and subscapular cataract, when the clouding is in the rear of the lens capsule.”

The study did not find a link between smoking and cortical cataract, a type of cataract in which the cortex of the lens is affected by cloudiness. Their findings have been published in the journal Investigative Ophthalmology & Visual Science (IOVS).

“Although cataracts can be removed surgically to restore sight, many people remain blind from cataracts due to inadequate surgical services and high surgery expenses,” Ye said. “Identifying modifiable risk factors for cataracts may help establish preventive measures and reduce the financial as well as clinical burden caused by the disease.”

“We think our analysis may inspire more high-quality epidemiological studies” the study author added. “Our analysis shows that association between smoking and the risk of age-related cataract differ by subtypes, suggesting that pathophysiologic processes may differ in the different cataract types.”

In a study that challenges the long-held notion that the primary function of sleep is to give rest to the brain, researchers have found that not getting enough shut-eye has a harmful impact on fat cells, reducing by 30 percent their ability to respond to insulin, a hormone that regulates energy.

Sleep deprivation has long been associated with impaired brain function, causing decreased alertness and reduced cognitive ability. The latest finding—published by University of Chicago Medicine researchers in the Oct. 16 issue of the Annals of Internal Medicine—is the first description of a molecular mechanism directly connecting sleep loss to the disruption of energy regulation in humans, a process that can lead over time to weight gain, diabetes and other health problems. The study suggests that sleep’s role in energy metabolism is at least as important as it is in brain function.

"We found that fat cells need sleep to function properly," said study author Matthew Brady, PhD, associate professor of medicine and vice-chair of the Committee on Molecular Metabolism and Nutrition at the University of Chicago.

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Assessing consciousness may seem like the ultimate exercise in subjectivity, but some researchers are moving closer to what they call an objective measure.

The goal is to provide clearer information for families with loved ones living in vegetative or minimally conscious states — conditions that are often caused by brain trauma or cardiac arrest.

“We really need to find a way to be able to measure consciousness reliably,” says Melanie Boly, a postdoctoral fellow at the Belgian National Fund for Research in Liege, Belgium. “For the family, this changes everything,” says Boly, who presented her team’s research on 14 October at the Society for Neuroscience meeting in New Orleans, Louisiana.

Vegetative patients make only reflexive movements and appear insensitive to their surroundings, while minimally conscious patients can make some purposeful movements and even feel pain. Clinically, the differences between these patients can be difficult even for experienced physicians to discern. But legally, the differences are clear.

In 2011, the UK court system denied a family’s request to end life support for their daughter after additional tests revised her initial diagnosis from ‘vegetative’ to ‘minimally conscious’.

To derive a numerical measure of consciousness, Boly and her colleagues pulsed subjects’ heads with a brief electromagnetic wave, then measured neural responses using electrodes stuck to the scalp.

In 32 healthy, awake people, the electromagnetic impulse sent complex patterns of electrical activity reverberating throughout the brain. In healthy sleeping people, or people under general anaesthesia, the brain displayed shorter, simpler responses that stayed closer to the site of the initial stimulation. The researchers quantified these differences in a measure of response complexity.

In six patients diagnosed as vegetative, the electromagnetic pulse elicited responses with complexity indices similar to those in sleeping or anaesthetized healthy subjects. Twelve minimally conscious patients showed slightly more complex responses. And two ‘locked-in’ patients — people who are fully conscious but unable to move or communicate — showed complexity indices similar to healthy, awake subjects.

Boly and her colleagues have previously noted some of these differences across patient groups but with poor reliability for individual patients. With the complexity index, which combines several aspects of the brain’s response, she says, “this is the first time we really have a measure that works at a single-subject level.”

“It’s not going to supplant a clinical assessment,” says Nicholas Schiff, a neurologist at the Weill Cornell Medical College in New York. But he says the complexity index could become a valuable tool for adding some certainty to the subjective process of evaluating patient consciousness.

“I personally would welcome a test that could provide us with objective measurements,” says David Okonkwo, clinical director of the Brain Trauma Research Center at the University of Pittsburgh in Pennsylvania. However, he said much more testing is needed to tell whether the complexity index meets that standard.

“We need more patients,” agrees Boly, “but it’s extremely promising.”

Rapamycin, a drug used to prevent rejection in transplants, could delay the onset of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This is the main conclusion of a study published in the Nature in which has collaborated the researcher Isidro Ferrer, head of the group of Neuropathology at the Bellvitge Biomedical Research Institute (IDIBELL) and the Bellvitge University Hospital and Full Professor of Pathological Anatomy at the University of Barcelona. The research was led by researchers from the International School for Advanced Studies (SISSA) in Trieste (Italy).

The collaboration of the research group led by Dr. Ferrer with SISSA researchers began five years ago when they observed that Parkinson’s patients showed a deficit in UCHL1 protein. At that time, researchers didn’t know what mechanism produced this deficit. To discover it a European project was launched. It was coordinated by the Italian researchers and participated by other European research groups, including the group led by Dr. Ferrer. The project, called Dopaminet, focused on how dopaminergic neurons (brain cells whose neurotransmitter is dopamine) are involved in Parkinson’s disease.

Contrary to most common hypothesis that a DNA fragment encodes a protein through a messenger RNA molecule, the researchers found that it also works in reverse. They found a balance between the protein and its mirror protein, which is configured in reverse, and they are mutually controlled. If the protein mirror is located in the nucleus of the cell, it does not interact with the protein, while if it is in the cytoplasm, then both of them interact.

In the case of Parkinson’s disease the protein UCHL1 appears reduced and also its mirror protein is localized in the nucleus, and in the cytoplasm. Thus, the researchers sought a method to extract the mirror protein from the nucleus and made it interact with the original UCHL1 protein. The authors found that rapamycin was able to extract them from the nucleus. The drug allows the two proteins, the UCHL1 and its mirror, hold together in the cytoplasm, which would correct the mistakes that occur in Parkinson’s disease.

This in vitro research has allowed describing a new unknown mechanism. It is necessary that the UCHL1 mirror protein should accumulate in the nucleus and escape from the cytoplasm and join the UCLH1 protein. The combination of both makes the system work.

"The rapamycin can not cure Parkinson’s disease, but it may delay the onset of neurodegenerative diseases such as Alzheimer’s and Parkinson’s itself. Rapamycin can protect and delay the beginning of these diseases. It can complete the treatment, but it should be combined with other existing treatments", explains Isidro Ferrer.

Anyway, it is still far its application in patients. The next step is to validate these results in animal models and study the effects of rapamycin in combination with other drugs.

Scientists are presenting new research on how the brain develops during the dynamic and vulnerable transition period from childhood to adulthood. The findings underscore the uniqueness of adolescence, revealing factors that may influence depression, decision-making, learning, and social relationships.

The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

The brain’s “reward system,” those brain circuits and structures that mediate the experience and pursuit of pleasure, figured prominently in several studies. The studies shed light on adolescents’ ability to control impulsivity and think through problems; reveal physical changes in the “social brain;” document connections between early home life and brain function in adolescence; and examine the impact of diet on depressive-like behavior in rodents.

Today’s new findings show that:

• Adolescents can throw impulsivity out the window when big rewards are at stake. The bigger the reward, the more thoughtful they can be, calling on important brain regions to gather and weigh evidence, and make decisions that maximize gains (BJ Casey, PhD).
• Rodents that receive an omega-3 fatty acid in their diets, from gestation through their early development, appear less vulnerable to depressive-like behaviors during adolescence (Christopher Butt, PhD).
• Depression in older adolescent boys may be associated with changes in communication between regions of the brain that process reward. At the same time, the study found possible connections between early emotional attachments — particularly with mothers — and later reward system function (Erika Forbes, PhD).
• Early cognitive stimulation appears to predict the thickness of parts of the human cortex in adolescence, and experiences at age four appear to have a greater impact than those at age eight (Martha Farah, PhD).
• During the span of adolescence, the volume of the “social brain” — those areas that deal with understanding other people — changes substantially, with notable gender differences (Kathryn Mills, BA).

"Advances in neuroscience continue to delve deeper and deeper into the unique and dynamically changing biology of the adolescent brain," said press conference moderator Jay Giedd, MD, of the National Institute of Mental Health, an expert on childhood and adolescent brain development. "The insights are beginning to elucidate the mechanisms that make the teen years a time of particular vulnerabilities but also a time of great opportunity."

Neuroscientists from New York University and the University of California, Irvine have isolated the “when” and “where” of molecular activity that occurs in the formation of short-, intermediate-, and long-term memories. Their findings, which appear in the journal the Proceedings of the National Academy of Sciences, offer new insights into the molecular architecture of memory formation and, with it, a better roadmap for developing therapeutic interventions for related afflictions.

“Our findings provide a deeper understanding of how memories are created,” explained the research team leader Thomas Carew, a professor in NYU’s Center for Neural Science and dean of NYU’s Faculty of Arts and Science. “Memory formation is not simply a matter of turning molecules on and off; rather, it results from a complex temporal and spatial relationship of molecular interaction and movement.”

Neuroscientists have previously uncovered different aspects of molecular signaling relevant to the formation of memories. But less understood is the spatial relationship between molecules and when they are active during this process.

To address this question, the researchers studied the neurons in Aplysia californica, the California sea slug. Aplysia is a model organism that is quite powerful for this type of research because its neurons are 10 to 50 times larger than those of higher organisms, such as vertebrates, and it possesses a relatively small network of neurons—characteristics that readily allow for the examination of molecular signaling during memory formation. Moreover, its coding mechanism for memories is highly conserved in evolution, and thus is similar to that of mammals, making it an appropriate model for understanding how this process works in humans.

The scientists focused their study on two molecules, MAPK and PKA, which earlier research has shown to be involved in many forms of memory and synaptic plasticity—that is, changes in the brain that occur after neuronal interaction. But less understood was how and where these molecules interacted.

To explore this, the researchers subjected the sea slugs to sensitization training, which induces increased behavioral reflex responsiveness following mild tail shock, or in this study, mild activation of the nerve form the tail. They then examined the subsequent molecular activity of both MAPK and PKA. Both molecules have been shown to be involved in the formation of memory for sensitization, but the nature of their interaction is less clear.

What they found was MAPK and PKA coordinate their activity both spatially and temporally in the formation of memories. Specifically, in the formation of intermediate-term (i.e., hours) and long-term (i.e., days) memories, both MAPK and PKA activity occur, with MAPK spurring PKA action. By contrast, for short-term memories (i.e., less than 30 minutes), only PKA is active, with no involvement of MAPK.

A study by researchers from Emory University and Indiana University found that the beneficial effects daily exercise can have on the regeneration of nerves also require androgens such as testosterone in both males and females. It is the first report of both androgen-dependence of exercise on nerve regeneration and of an androgenic effect of exercise in females.

"The findings will provide a basis for the development of future treatment strategies for patients suffering peripheral nerve injuries," said Dale Sengelaub, professor in the Department of Psychological and Brain Sciences at IU. "And they underscore the need to tailor those treatments differently for men and women."

The researchers discussed the study on Monday at the Neuroscience 2012 scientific meeting in New Orleans.

Injuries to peripheral nerves are common. Hundreds of thousands of Americans are victims of traumatic injuries each year, and non-traumatic injuries, such as carpal tunnel syndrome, are found in even higher numbers. The researchers previously showed that two weeks of moderate daily exercise substantially improves regeneration of cut nerves and leads to functional recovery in mice, though different types of exercise are required to produce the effect in males and females. They now report that these beneficial effects of exercise require androgens such as testosterone in both males and females.

In the study they conducted, they exercised three groups of male and female mice. Nerves of the three groups were cut and surgically repaired. Once group received the drug flutamide, which blocks the androgen receptor. A second group received a placebo treatment. The third group was unexercised. Regenerating nerve fibers in the placebo group grew to more than twice the length of those in unexercised mice in both males and females. In flutamide-treated mice, the effects of exercise were blocked completely in both sexes.

The Society of Neuroscience is promoting the study (“Enhancement of peripheral axon regeneration by exercise requires androgen receptor signaling in both male and female mice”) to media covering the conference as a “Hot Topic.”

(Credit: Oleg Zabielin / Shutterstock)

A new study in animals shows that chronic stress during pregnancy prevents brain benefits of motherhood, a finding that researchers suggest could increase understanding of postpartum depression.

Rat mothers showed an increase in brain cell connections in regions associated with learning, memory and mood. In contrast, the brains of mother rats that were stressed twice a day throughout pregnancy did not show this increase.

The researchers were specifically interested in dendritic spines – hair-like growths on brain cells that are used to exchange information with other neurons.

Previous animal studies conducted by lead author Benedetta Leuner of Ohio State University showed that an increase of dendritic spines in new mothers’ brains was associated with improved cognitive function on a task that requires behavioral flexibility – in essence, enabling more effective multitasking. The dendritic spines increased by about 20 percent in these brain regions in new mothers, according to her findings.

The stress in this new study negated those brain benefits of motherhood, causing the stressed rats’ brains to match brain characteristics of animals that had no reproductive or maternal experience.

The stressed rats also had less physical interaction with their babies than did unstressed rats, a behavior observed in human mothers who experience postpartum depression.

“Animal mothers in our research that are unstressed show an increase in the number of connections between neurons. Stressed mothers don’t,” said Leuner, assistant professor of psychology and neuroscience at Ohio State and lead author of the study. “We think that makes the stressed mothers more vulnerable. They don’t have the capacity for brain plasticity that the unstressed mothers do, and somehow that’s contributing to their susceptibility to depression.”

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A new finding could lead to strategies for treating speech loss after a stroke and helping children with dyslexia.

New research links motor skills and perception, specifically as it relates to a second finding—a new understanding of what the left and right brain hemispheres “hear.” Georgetown University Medical Center researchers say these findings may eventually point to strategies to help stroke patients recover their language abilities, and to improve speech recognition in children with dyslexia.

The study, presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience, is the first to match human behavior with left brain/right brain auditory processing tasks. Before this research, neuroimaging tests had hinted at differences in such processing.

“Language is processed mainly in the left hemisphere, and some have suggested that this is because the left hemisphere specializes in analyzing very rapidly changing sounds,” says the study’s senior investigator, Peter E. Turkeltaub, M.D., Ph.D., a neurologist in the Center for Brain Plasticity and Recovery. This newly created center is a joint program of Georgetown University and MedStar National Rehabilitation Network.

Turkeltaub and his team hid rapidly and slowly changing sounds in background noise and asked 24 volunteers to simply indicate whether they heard the sounds by pressing a button.

“We asked the subjects to respond to sounds hidden in background noise,” Turkeltaub explained. “Each subject was told to use his or her right hand to respond during the first 20 sounds, then the left hand for the next 20 second, then right, then left, and so on.”

He says when a subject was using their right hand, they heard the rapidly changing sounds more often than when they used their left hand, and vice versa for the slowly changing sounds.

“Since the left hemisphere controls the right hand and vice versa, these results demonstrate that the two hemispheres specialize in different kinds of sounds—the left hemisphere likes rapidly changing sounds, such as consonants, and the right hemisphere likes slowly changing sounds, such as syllables or intonation,” Turkeltaub explains.

“These results also demonstrate the interaction between motor systems and perception. It’s really pretty amazing. Imagine you’re waving an American flag while listening to one of the presidential candidates. The speech will actually sound slightly different to you depending on whether the flag is in your left hand or your right hand.”

Ultimately, Turkeltaub hopes that understanding the basic organization of auditory systems and how they interact with motor systems will help explain why language resides in the left hemisphere of the brain, and will lead to new treatments for language disorders, like aphasia (language difficulties after stroke or brain injury) or dyslexia.

“If we can understand the basic brain organization for audition, this might ultimately lead to new treatments for people who have speech recognition problems due to stroke or other brain injury. Understanding better the specific roles of the two hemispheres in auditory processing will be a big step in that direction. If we find that people with aphasia, who typically have injuries to the left hemisphere, have difficulty recognizing speech because of problems with low-level auditory perception of rapidly changing sounds, maybe training the specific auditory processing deficits will improve their ability to recognize speech,” Turkeltaub concludes.

Scientists at Wake Forest Baptist Medical Center have taken the first steps to create neural-like stem cells from muscle tissue in animals. Details of the work are published in two complementary studies published in the September online issues of the journals Experimental Cell Research and Stem Cell Research.

“Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can’t harvest neural stem cells from the brain or spinal cord without harming the donor,” said Osvaldo Delbono, M.D., Ph.D., professor of internal medicine at Wake Forest Baptist and lead author of the studies.

“Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumors and other diseases, although more studies are needed.”

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice (PLOS One, Feb.3, 2011).

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumors, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumors were found.

“Right now, patients with glioblastomas or other brain tumors have very poor outcomes and relatively few treatment options,” said Alexander Birbrair, a doctoral student in Delbono’s lab and first author of these studies. “Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumors but also for other central nervous system diseases.”

In addition, the Wake Forest Baptist team is now conducting research to determine if these neural-like cells also have the capability to become functioning neurons in the central nervous system.

A paper by Shizhong Han and colleagues in the current issue of Biological Psychiatry implicates a new gene in the risk for cannabis dependence. This gene, NRG1, codes for the ErbB4 receptor, a protein implicated in synaptic development and function.

The researchers set out to investigate susceptibility genes for cannabis dependence, as research has already shown that it has a strong genetic component.

To do this, they employed a multi-stage design using genetic data from African American and European American families. In the first stage, a linkage analysis, the strongest signal was identified in African Americans on chromosome 8p21. Then using a genome-wide association study dataset, they identified one genetic variant at NRG1 that showed consistent evidence for association in both African Americans and European Americans. Finally, they replicated the association of that same variant in an independent sample of African-Americans.

All together, the findings suggest that NRG1 may be a susceptibility gene for cannabis dependence.

An interesting feature of this paper is that these findings may also suggest a link between the genetics of schizophrenia and the genetics of cannabis dependence. NRG1 emerged into public awareness after a series of genetic studies implicated it in the heritable risk for schizophrenia. Subsequent studies in post-mortem brain tissue also suggested that the regulation of NRG1 was altered in the brains of individuals diagnosed with schizophrenia.

Thus, the current findings may help to explain the already established link between cannabis use and the risk for developing schizophrenia. A number of epidemiologic studies have attributed the association of cannabis use and schizophrenia to the effects of cannabis on the brain rather than a common genetic link between these two conditions.

"The current data provide a potentially important insight into the heritable risk for schizophrenia and raise the possibility that there are some common genetic contributions to these two disorders," commented Dr. John Krystal, Editor of Biological Psychiatry.

However, further research will be necessary to further confirm the role that NRG1 plays in cannabis dependence and the potential link between cannabis use and psychosis.

Scientists have proved a 60-year-old theory about how nerve signals are sent around the body at varying speeds as electrical impulses.

Researchers tested how these signals are transmitted through nerve fibres, which enables us to move and recognise sensations such as touch and smell.

The findings from the University of Edinburgh have validated an idea first proposed by Nobel laureate Sir Andrew Huxley.

It has been known for many years that an insulating layer – known as myelin – which surrounds nerve fibres is crucial in determining how quickly these signals are sent.

This insulating myelin is interrupted at regular intervals along the nerve by gaps called nodes.

Scientists, whose work was funded by the Wellcome Trust, have now proved that the longer the distance between nodes, the quicker the nerve fibres send signals down the nerves.

The theory that the distance between these gaps might affect the speed of electrical signals was first proposed by Sir Andrew Huxley, who won the Nobel Prize in 1963 for his work on electrical signalling in the nervous system, and who died earlier this year.

The study, published in the journal Current Biology, will help provide insight into what happens in people with nerve damage. It will also shed light on how nerves develop before and after birth.

Professor Peter Brophy, Director of the University of Edinburgh’s Centre for Neuroregeneration, said: “The study gives us greater insight into how the central and peripheral nervous systems work and what happens after nerves become injured. We know that peripheral nerves have the capacity to repair, but shorter lengths of insulation around the nerve fibres after repair affect the speed with which impulses are sent around the body.”

The researchers found that when the myelin reached a certain length, the speed with which nerves impulses were conducted reached a peak.

The study, carried out in mice, also confirmed that a protein – periaxin – plays a key role in regulating the length of myelin layers around nerve fibres.

Washington State University researchers have developed a new drug candidate that dramatically improves the cognitive function of rats with Alzheimer’s-like mental impairment.

Their compound, which is intended to repair brain damage that has already occurred, is a significant departure from current Alzheimer’s treatments, which either slow the process of cell death or inhibit cholinesterase, an enzyme believed to break down a key neurotransmitter involved in learning and memory development.

Such drugs, says Joe Harding, a professor in WSU’s College of Veterinary Medicine, are not designed to restore lost brain function, which can be done by rebuilding connections between nerve cells.

"This is about recovering function,” he says. "That’s what makes these things totally unique. They’re not designed necessarily to stop anything. They’re designed to fix what’s broken. As far as we can see, they work.”

Harding, College of Arts and Sciences Professor Jay Wright and other WSU colleagues report their findings in the online “Fast Forward” section of the Journal of Pharmacology and Experimental Therapeutics.

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Three studies conducted as part of Wayne State University’s Systems Biology of Epilepsy Project (SBEP) could result in new types of treatment for the disease and, as a bonus, for behavioral disorders as well.

The SBEP started out with funds from the President’s Research Enhancement Fund and spanned neurology, neuroscience, genetics and computational biology. It since has been supported by multiple National Institutes of Health-funded grants aimed at identifying the underlying causes of epilepsy, and it is uniquely integrated within the Comprehensive Epilepsy Program at the Wayne State School of Medicine and the Detroit Medical Center.

Under the guidance of Jeffrey Loeb, M.D., Ph.D., associate director of the Center for Molecular Medicine and Genetics (CMMG) and professor of neurology, the project brings together researchers from different fields to create an interdisciplinary research program that targets the complex disease. The multifaceted program at Wayne State is like no other in the world, officials say, with two primary goals: improving clinical care and creating novel strategies for diagnosis and treatment of patients with epilepsy.

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