Posts tagged science

May 2, 2012

Collaborative research by groups headed by scientists Joan J. Guinovart and Marco Milán at the Institute for Research in Biomedicine (IRB Barcelona) has revealed conclusive evidence about the harmful effects of the accumulation of glucose chains (glycogen) in fly and mouse neurons.

This image shows a cerebellum sample from a healthy mouse. Credit: Jordi Duran (IRB Barcelona)

These two animal models will allow scientists to address the genes involved in this harmful process and to find pharmacological solutions that allow disintegration of the accumulations or limitation of glycogen production. Advances in this direction would make a significant contribution to investigation into Lafora progressive myoclonic epilepsy and other neurodegenerative diseases characterized by glycogen accumulation in neurons. The journal EMBO Molecular Medicine publishes the results of the study this week.

This image shows the same tissue (mouse cerebellum) after glycogen accumulation. Credit: Jordi Duran (IRB Barcelona)

"Our data clearly indicate that glycogen accumulation alone kills neurons and thus dramatically reduces lifespan", explains Guinovart, an expert in glycogen metabolism, group leader at IRB Barcelona, and senior professor at the University of Barcelona, "because the only thing we have manipulated in the neurons is their capacity to produce glycogen".

The inclusion of the Drosophila fly in the study provides in vivo confirmation of the theory in another animal model as these flies also show the same symptoms of degeneration as mice when glycogen accumulates in neurons. However, in addition the use of Drosophila will speed up obtaining genetic data and the screening of therapeutic molecules. “In a short time we will be able to perform a massive search for genes involved in the pathological process and to understand it better at the molecular level”, emphasizes Marco Milán, ICREA researcher at IRB Barcelona and a specialist inDrosophila. “But the flies will also be useful to identify pharmacological molecules that can cure”, he explains.

The IRB Barcelona teams are designing several experiments to identify the possible therapeutic targets that may be useful to prevent glycogen accumulation in neurons. In addition to the direct relation to Lafora epilepsy, a progressive degenerative disease that affects adolescents and has no cure, glycogen accumulation could be the main cause of other neurodegenerative illnesses such as Adult polyglucosan body disease and Andersen’s disease.

Provided by Institute for Research in Biomedicine (IRB Barcelona)

Source: medicalxpress.com

May 1, 2012

Scientists now have a better understanding of how precise memories are formed thanks to research led by Prof. Jean-Claude Lacaille of the University of Montreal’s Department of Physiology. “In terms of human applications, these findings could help us to better understand memory impairments in neurodegenerative disorders like Alzheimer’s disease,” Lacaille said.

The study looks at the cells in our brains, or neurons, and how they work together as a group to form memories. Chemical receptors at neuron interconnections called synapses enable these cells to form electrical networks that encode memories, and neurons are classified into two groups according to the type of chemical they produce: excitatory, who produce chemicals that increase communication between neurons, and inhibitory, who have the opposite effect, decreasing communication. “Scientists knew that inhibitory cells enable us to refine our memories, to make them specific to a precise set of information,” Lacaille explained. “Our findings explain for the first time how this happens at the molecular and cell levels.”

Many studies have been undertaken on excitatory neurons, but very little research has been done on inhibitory neurons, partly because they are very difficult to study. The scientists found that a factor called “CREB” plays a key role in adjusting gene expression and the strength of synapses in inhibitory neurons. Proteins are biochemical compounds encoded in our genes that enable cells to perform their various functions, and new proteins are necessary for memory formation. “We were able to study how synapses of inhibitory neurons taken from rats are modified in the 24 hours following the formation of a memory,” Lacaille said. “In the laboratory, we simulated the formation of a new memory by using chemicals. We then measured the electrical activity within the network of cells. In cells where we had removed CREB, we saw that the strength of the electrical connections was much weaker. Conversely, when we increased the presence of CREB, the connections were stronger.”

This new understanding of the chemical functioning of the brain may one day lead to new treatments for disorders like Alzheimer’s, as researchers will be able to look at these synaptic mechanisms and design drugs that target the chemicals involved. “We knew that problems with synapse modifications are amongst the roots of the cognitive symptoms suffered by the victims of neurodegenerative diseases,” Lacaille said. “These findings shine light on the neurobiological basis of their memory problems. However, we are unfortunately many years away from developing new treatments from this information.”

The findings were published in the Journal of Neuroscience on May 2, 2012. The researchers received funding from the Canadian Institutes of Health Research and the Fonds de recherche du Québec – Santé. Jean-Claude Lacaille is the Canada Research Chair in Cellular and Molecular Neurophysiology. Israeli Ran, recipient of a Fellowship of the Savoy Foundation, and Isabel Laplante contributed to this research. All three researchers were affiliated with the Department of Physiology and the Groupe de Recherche sur le Système Nerveux Central of the University of Montreal when the research was undertaken. The University of Montreal is officially known as Université de Montréal.

Provided by University of Montreal 

Source: medicalxpress.com

ScienceDaily (May 1, 2012) — Barrow Neurological Institute researchers Jorge Otero-Millan, Stephen Macknik, and Susana Martinez-Conde share the recent cover of the Journal of Neuroscience in a compelling study into why illusions trick our brains. Barrow is part of St. Joseph’s Hospital and Medical Center in Phoenix.

The study, led by Martinez-Conde’s laboratory, explores the neural bases of illusory motion in Akiyoshi Kitaoka’s striking visual illusion, known as the “Rotating Snakes.” Kitaoka is a Japanese psychology professor who specializes in visual illusions of geometric shapes and motion illusions.

The study shows that tiny eye movements and blinking can make a geometric drawing of “snakes” appear to dance. The results help explain the mystery of how the Rotating Snakes illusion tricks the brain.

"Visual illusions demonstrate the ways in which the brain creates a mental representation that differs from the physical world," says Martinez-Conde. "By studying illusions, we can learn the mechanisms by which the brain constructs our conscious experience of the world."

Earlier studies of the “Rotating Snakes” indicated the perception of motion was triggered by the eyes moving slowly across the illusion. But by tracking eye movements in eight volunteers, the vision neuroscientists found a different explanation: fast eye movements called “saccades,” some of which are microscopic and undetectable by the viewer, drive the illusory motion.

Participants lifted a button when the snakes seemed to swirl and pressed down the button when the snakes appeared still. Right before the snakes appeared to move, participants tended to produce blinks, saccades and/or microsaccades, and right before the snakes stopped, participants’ eyes tended to remain stable, Otero-Millan, Macknik, and Martinez-Conde report in the April 25th Journal of Neuroscience cover story.

"Studying the mismatch between perception and reality may lead to a deeper understanding of the mind," says Martinez-Conde. "The findings from our recent study may help us to understand the neural bases of motion perception, both in the normal brain, and in patients with brain lesions that affect the perception of motion. This research could aid in the design of neural prosthetics for patients with brain damage."

Source: Science Daily

ScienceDaily (May 1, 2012) — Scientists at Joslin Diabetes Center have identified a key mechanism of action for the TOR (target of rapamycin) protein kinase, a critical regulator of cell growth which plays a major role in illness and aging. This finding not only illuminates the physiology of aging but could lead to new treatments to increase lifespan and control age-related conditions, such as cancer, type 2 diabetes, and neurodegeneration.

Over the past decade, studies have shown that inhibiting TOR activity, which promotes cell growth by regulating protein synthesis, increases lifespan in a variety of species including flies and mice; in recent years research has focused on uncovering the precise mechanisms underlying this effect. The Joslin study, published in the May 2 issue of Cell Metabolism, reports that TOR has a direct impact on two master gene regulator proteins — SKN-1 and DAF-16 -which control genes that protect against environmental, metabolic and proteotoxic stress. The TOR kinase acts in two signaling pathways, TORC1 and TORC2. When TORC1 is inhibited, SKN-1 and DAF-16 are mobilized, leading to activation of protective genes that increase stress resistance and longevity. This new finding was demonstrated in experiments with C. elegans, a microscopic worm used as a model organism, but activation of protective genes was also observed in mice. Most findings in C. elegans have turned out to be applicable to mice and humans.

"We uncovered a critical mechanism in the relationship between TOR and aging and disease. There is a homeostatic relationship between protein synthesis and stress defenses: when protein synthesis is reduced, stress defenses increase," says lead author T. Keith Blackwell, MD, PhD, co-head of the Joslin Islet Cell & Regenerative Biology Section and Professor of Pathology at Harvard Medical School. The Blackwell lab studies the aging process and how it is influenced by insulin and other metabolic regulatory mechanisms.

TOR activity, which is essential for early development but can lead to age-related decline, is implicated in a variety of chronic diseases, including diabetes, cardiovascular disease, cancer and neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. In diabetes, TOR has both positive and negative effects: It promotes beta cell growth and insulin production but inappropriate TORC1 activity leads to insulin resistance and beta cell demise, as well as fat accumulation. At the same time, insufficient TORC2 activity can lead to insulin resistance.

The new results on TOR and SKN-1 suggest that SKN-1 might have a positive effects in Type 2 diabetes: “Turning on this pathway could be important in defending against the effects of high glucose, and promoting beta cell health” says Blackwell.

In the study, TOR activity was inhibited by genetic interference and the TOR-inhibitor rapamycin, a naturally occurring compound which is used as an immunosuppressant in organ transplants, and has been shown to increase lifespan in mice. Using rapamycin or related drugs to treat diseases affected by TOR has been a subject of intense interest among scientists and clinicians. The study found that rapamycin inhibits both TORC1 and TORC2, which will interest scientists investigating rapamycin as a pharmaceutical. “We need to increase understanding of rapamycin and its effects on TOR activity to determine how targeting TOR or processes it controls can help treat diseases that involve TOR and derangement of metabolism. We also need to look at therapies that work on TORC1 and TORC2 independently,” said Blackwell. However, one caveat with TOR inhibition is that the kinase plays such a central role in the basic physiology of growing and dividing cells. The new results suggest that in some situations we might want to bypass TOR itself, and directly harness beneficial processes that are controlled by SKN-1 or DAF-16.

Future research will focus on gaining a deeper understanding of how TOR acts on beneficial defense pathways and affects aging and disease. “In science, we are always looking for ways to interfere with mechanisms that promote aging and disease in ways that are beneficial to people,” says Blackwell.

Source: Science Daily

May 1, 2012

You think your computer has a lot of memory … if you keep using your computer you may, too.

Combining mentally stimulating activities, such as using a computer, with moderate exercise decreases your odds of having memory loss more than computer use or exercise alone, a Mayo Clinic study shows. Previous studies have shown that exercising your body and your mind will help your memory but the new study, published in the May 2012 issue of Mayo Clinic Proceedings, reports a synergistic interaction between computer activities and moderate exercise in “protecting” the brain function in people better than 70 years old.

Researchers studies 926 people in Olmsted County, Minn., ages 70 to 93, who completed self-reported questionnaires on physical exercise, and computer use within one year prior of the date of interview. Moderate physical exercise was defined as brisk walking, hiking, aerobics, strength training, golfing without a golf cart, swimming, doubles tennis, yoga, martial arts, using exercise machines and weightlifting. Mentally stimulating activities included reading, crafts, computer use, playing games, playing music, group and social and artistic activities and watching less television. Of those activities the study singled out computer use because of its popularity, said study author Yonas E. Geda, M.D., MSc, a physician scientist with Mayo Clinic in Arizona.

"The aging of baby boomers is projected to lead to dramatic increases in the prevalence of dementia," Dr. Geda said. "As frequent computer use has becoming increasingly common among all age groups, it is important to examine how it relates to aging and dementia. Our study further adds to this discussion."

The study examined exercise, computer use and the relationship to neurological risks such as mild cognitive impairment, Dr. Geda says. Mild cognitive impairment is the intermediate stage between normal memory loss that comes with aging and early Alzheimer’s disease. Of the study participants who did not exercise and did not use a computer, 20.1 percent were cognitively normal and 37.6 percent showed signs of mild cognitive impairment. Of the participants who both exercise and use a computer, 36 percent were cognitively normal and 18.3 percent showed signs of MCI.

Dr. Geda expects that this study will lead to more research on this topic.

Provided by Mayo Clinic

Source: medicalxpress.com

ScienceDaily (Apr. 30, 2012) — Migraine pain sits at the upper end of the typical pain scale — an angry-red section often labeled “severe.” At this intensity, pain is debilitating. Yet many sufferers do not get relief from — or cannot tolerate — over-the-counter and commonly prescribed pain medications.

Migraine Therapy: Computer model of the distribution of electrical current in the brain’s pain network (sub-cortical and brainstem structures) during transcranial direct current stimulation (tDCS). (Credit: Image courtesy of City College of New York)

Recently, a team of researchers that includes Dr. Marom Bikson, associate professor of biomedical engineering in CCNY’s Grove School of Engineering, has shown that a brain stimulation technology can prevent migraine attacks from occurring. Their technique, using transcranial direct current stimulation (tDCS), applies a mild electrical current to the brain from electrodes attached to the scalp.

"We developed this technology and methodology in order to get the currents deep into the brain," said Bikson. The researchers aimed to tap into the so-called pain network, among other areas, a collection of interconnected brain regions involved in perceiving and regulating pain.

Professor Bikson and his colleagues, including Dr. Alexandre DaSilva at the University of Michigan School of Dentistry and Dr. Felipe Fregni at Harvard Medical School, found that the technology seems to reverse ingrained changes in the brain caused by chronic migraine, such as greater sensitivity to headache triggers.

Repeated sessions reduced the duration of attacks and decreased the pain intensity of migraines that did occur on average about 37 percent. The improvements accumulated over four weeks of treatment and they persisted.

In pilot studies, the effects lasted for months. The only side effect subjects reported was a mild tingling sensation during treatment. Professor Bikson expects that a patient could use the system every day to ward off attacks, or periodically, like a booster.

The team’s computational models show that tDCS delivers therapeutic current along the pain network through both upper (cortical) and deep brain structures. They will publish their results in the journal Headache.

Thirty-six million Americans suffer from migraine, according to the Migraine Research Foundation. Of these, 14 million of them experience chronic daily headaches. “The fact that people still suffer from migraines means that the existing treatments using electrical technology or chemistry are not working,” said Professor Bikson.

Existing brain stimulation technologies can help relieve a migraine already underway. But those afflicted with chronic migraine pain may suffer 15 or more attacks a month, making treatment a constant battle.

The other techniques also have drawbacks — from heavy, unwieldy equipment to serious side effects, such as seizures. Some only stimulate the upper layers of the brain. Others reach deep brain regions, but require brain surgery to implant the electrodes. The tDCS technology is safe, easy to use, and portable, Professor Bikson said. “You can walk around with it and keep it in your desk drawer or purse. This is definitely the first technology that operates on just a 9-volt battery and can be applied at home.” He envisions future units as small as an iPod.

The next step will be to scale up clinical trials to a larger study population. A market-ready version of the tDCS is still years away. “There’s something about migraine pain that’s particularly distressing,” noted Professor Bikson. “If it’s possible to help some people get just 30 percent better, that’s a very meaningful improvement in quality of life.”

Source: Science Daily

ScienceDaily (Apr. 30, 2012) — Researchers studying multiple sclerosis (MS) have long been looking for the specific molecules in the body that cause lesions in myelin, the fatty, insulating cells that sheathe the nerves. Nearly a decade ago, a group at Mayo Clinic found a new enzyme, called Kallikrein 6, that is present in abundance in MS lesions and blood samples and is associated with inflammation and demyelination in other neurodegenerative diseases. In a study published this month in Brain Pathology,the same group found that an antibody that neutralizes Kallikrein 6 is capable of staving off MS in mice.

"We were able to slow the course of disease through early chronic stages, both in the brain and spinal cord," says lead author Isobel Scarisbrick, Ph.D., of the Mayo Clinic Department of Physical Medicine and Rehabilitation.

Researchers looked at mice representing a viral model of MS. The model is based on the theory that infection with viral infection early in life results in an eventual abnormal immune response in the brain and spinal cord. One week after being infected with a virus, the mice showed elevated levels of Kallikrein 6 enzyme in the brain and spinal cord. However, when researchers treated mice to produce an antibody capable of blocking and neutralizing the enzyme, they saw a decrease in diseases effecting the brain and spinal cord, including demyelination. The Kallikrein 6 neutralizing antibody had reduced inflammatory white blood cells and slowed the depletion of myelin basic protein, a key component of the myelin sheath.

The findings in the MS model have implications for other conditions affecting the brain and spinal cord. The group has previously shown that the Kallikrein 6 enzyme, produced by immune cells, is elevated in spinal cord injury, while other studies have shown it to be elevated in animal models of stroke and patients with post-polio syndrome.

"These findings suggest Kallikrein 6 plays a role in the inflammatory and demyelinating processes that accompany many types of neurological conditions," says Dr. Scarisbrick. "In the early chronic stages of some neurological diseases, Kallikrein 6 may represent a good molecule to target with drugs capable of neutralizing its effects."

Source: Science Daily

ScienceDaily (Apr. 30, 2012) — UC Davis researchers have found novel compounds that disrupt the formation of amyloid, the clumps of protein in the brains of people with Alzheimer’s disease believed to be important in causing the disease’s characteristic mental decline. The so-called “spin-labeled fluorene compounds” are an important new target for researchers and physicians focused on diagnosing, treating and studying the disease.

The study was published April 30 in the online journal PLoS ONE.

"We have found these small molecules to have significant beneficial effects on cultured neurons, from protecting against toxic compounds that form in neurons to reducing inflammatory factors," said John C. Voss, professor of biochemistry and molecular medicine at the UC Davis School of Medicine and the principal investigator of the study. "As a result, they have great potential as a therapeutic agent to prevent or delay injury in individuals in the earliest stages of Alzheimer’s disease, before significant damage to the brain occurs."

Amyloid is an accumulation of proteins and peptides that are otherwise found naturally in the body. One component of amyloid − the amyloid beta (Aβ) peptide − is believed to be primarily responsible for destroying neurons in the brain. Fluorene compounds, which are small three-ringed molecules, originally were developed as imaging agents to detect amyloid with PET imaging. In addition to being excellent for detecting amyloid, fluorenes bind and destabilize Aβ peptide and thereby reduce amyloid formation, according to previous findings in mice by Lee-Way Jin, another study author and associate professor in the UC Davis MIND Institute and Department of Medical Pathology and Laboratory Medicine.

The current research studied the effects of fluorene compounds by attaching a special molecule to make their activity evident using electron paramagnetic resonance (EPR) spectroscopy. This technology allows researchers to observe very specific activities of molecules of interest because biological tissues do not emit signals detectable by EPR. Since Voss was interested in the activity of fluorenes, he added a nitroxide “spin label,” a chemical species with a unique signal that can be measured by EPR.

The group found that spin-labeled compounds disrupted Aβ peptide formation even more effectively than did non-labeled fluorenes. In addition, the antioxidant properties of the nitroxide, which scavenge reactive oxygen species known to damage neurons and increase inflammation, significantly contributed to the protective effects on neurons.

"The spin-labeled fluorenes demonstrated a number of extremely important qualities: They are excellent for detecting amyloid in imaging studies, they disrupt Aβ formation, and they reduce inflammation," said Voss. "This makes them potentially useful in the areas of research, diagnostics and treatment of Alzheimer’s disease."

Alzheimer’s disease is the most common form of dementia and affects some 5 million Americans. Current medications used to fight the disease usually have only small and temporary benefits, and commonly have many side effects.

A major obstacle in developing Alzheimer’s disease therapy is that most molecules will not cross the blood-brain barrier, so that potential treatments given orally or injected into the bloodstream cannot enter the brain where they are needed. Fluorene compounds are small molecules that have been shown to penetrate the brain well.

"We have brought together expertise from diverse fields to get to this point, and what was once a side interest has become a major focus," said Voss. "We are very excited and hopeful that these unique compounds can become extremely important."

Voss’ group next plans to study the safety of spin-labeled fluorene compounds as well as their efficacy for treating models of Alzheimer’s disease in small animals.

Source: Science Daily

April 30, 2012

A Northwestern University study that will be published in the Proceedings of the National Academy of Sciences (PNAS) provides the first biological evidence that bilinguals’ rich experience with language in essence “fine-tunes” their auditory nervous system and helps them juggle linguistic input in ways that enhance attention and working memory.

Northwestern bilingualism expert Viorica Marian teamed up with auditory neuroscientist Nina Kraus to investigate how bilingualism affects the brain. In particular, they looked at subcortical auditory regions that are bathed with input from cognitive brain areas. In extensive research, Kraus has already shown that lifelong music training enhances language processing, and an examination of subcortical auditory regions helped to tell that tale.

"For our first collaborative study, we asked if bilingualism could also promote experience-dependent changes in the fundamental encoding of sound in the brainstem — an evolutionarily ancient part of the brain," said Marian, professor of communication sciences in Northwestern’s School of Communication. The answer, according to their study, is a resounding yes.

The researchers found that the experience of bilingualism changes how the nervous system responds to sound. “People do crossword puzzles and other activities to keep their minds sharp,” Marian said. “But the advantages we’ve discovered in dual language speakers come automatically simply from knowing and using two languages. It seems that the benefits of bilingualism are particularly powerful and broad, and include attention, inhibition and encoding of sound.”

Co-authored by Kraus, Marian and researchers Jennifer Krizman, Anthony Shook and Erika Skoe, “Bilingualism and the Brain: Subcortical Indices of Enhanced Executive Function” underscores the pervasive impact of bilingualism on brain development. The article will appear in the April 30 issue of PNAS.

"Bilingualism serves as enrichment for the brain and has real consequences when it comes to executive function, specifically attention and working memory," said Kraus, Hugh Knowles Professor at Northwestern. In future studies, she and Marian will investigate whether these results can be achieved by learning a language later in life.

In the study, the researchers recorded the brainstem responses to complex sounds (cABR) in 23 bilingual English-and-Spanish-speaking teenagers and 25 English-only-speaking teens as they heard speech sounds in two conditions.

Under a quiet condition, the groups responded similarly. But against a backdrop of background noise, the bilingual brains were significantly better at encoding the fundamental frequency of speech sounds known to underlie pitch perception and grouping of auditory objects. This enhancement was linked with advantages in auditory attention.

"Through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound," Kraus explained.

"Bilinguals are natural jugglers," said Marian. "The bilingual juggles linguistic input and, it appears, automatically pays greater attention to relevant versus irrelevant sounds. Rather than promoting linguistic confusion, bilingualism promotes improved ‘inhibitory control,’ or the ability to pick out relevant speech sounds and ignore others."

The study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. “The bilingual’s enhanced experience with sound results in an auditory system that is highly efficient, flexible and focused in its automatic sound processing, especially in challenging or novel listening conditions,” Kraus added.

Provided by Northwestern University

Source: medicalxpress.com

ScienceDaily (Apr. 30, 2012) — University of Iowa biologists have advanced the knowledge of human neurodevelopmental disorders by finding that a lack of a particular group of cell adhesion molecules in the cerebral cortex — the outermost layer of the brain where language, thought and other higher functions take place — disrupts the formation of neural circuitry.

Reconstructions of single wildtype (left) and gamma-protocadherin mutant (right) cortical neurons are superimposed upon a low magnification view of fluorescently-labeled neurons in the corresponding animals. (Credit: Image courtesy of University of Iowa Health Care)

Andrew Garrett, former neuroscience graduate student and current postdoctoral fellow at the Jackson Laboratory, Bar Harbor, Maine; Dietmar Schreiner, former postdoctoral fellow currently at the University of Basel, Switzerland; Mark Lobas, current neuroscience graduate student; and Joshua A. Weiner, associate professor in the UI College of Liberal Arts and Sciences Department of Biology, published their findings in the April 26 issue of the journal Neuron.

Cell adhesion is the way in which cells “hold hands” — how one cell binds itself to another cell using specific molecules that protrude from cell membranes and bind each other together. The process is necessary to form all body tissues. The UI researchers studied a clustered family of 22 genes (gamma-protocadherins) that make such cellular hand-holding possible by encoding cell adhesion molecules.

In their previous work, they found that mice lacking the molecules exhibited death of neurons and loss of synapses in the spinal cord. So, they knew the gamma-protocadherins were important for neurons in the spinal cord, but not whether this was true in the cortex. However, in the current study, they found that an absence of the cell adhesion molecules had a significant and much different effect.

"We found that mice lacking the gamma-protocadherins in the cortex do not exhibit the severe loss of synapses and increased neuronal death that we observed in the spinal cord," says Weiner. "Instead, we found that the cortical neurons had severely reduced development of their dendrites, tree-like branched structures that receive input from other neurons.

"We discovered the reason for this: gamma-protocadherins normally inhibit a key signaling pathway within neurons that acts to reduce dendrite branching. In the absence of the gamma-protocadherins, this signaling pathway was hyperactive, leading to defective branching of cortical neuron dendrites," says Weiner.

In their previous work, the researchers showed that these molecules — the 22 distinct adhesion molecules, the gamma-protocadherins — are critical for the development of the animal, because when all of the genes are deleted from mice, they die shortly after birth with a variety of neurological defects including loss of connections (synapses) and excessive neuronal cell death in the spinal cord — an early-developing part of the nervous system.

Because those mutants die so young, the researchers could not assess a role for the gamma-protocadherins in the cerebral cortex. The reason is that the cortex develops only after birth. They used new genetic technologies to remove the gamma-protocadherins only from the cerebral cortex, which allowed the animals to survive to adulthood.

Weiner says that the latest research findings may help researchers to better understand the causes of various human developmental disorders.

"Human neurodevelopmental disorders such as autism, mental retardation, and schizophrenia all involve dysregulation of dendrite branching and synaptogenesis," he says. "Our identification of a large family of 22 cell adhesion molecules — which we previously showed interact with each other in very complex and specific ways — as new regulators of dendrite branching raises the question of whether specific interactions between distinct neuronal groups during development is important for the spreading of dendritic branches. If so, the gamma-protocadherins and/or the signaling pathways they regulate might be disrupted in a variety of human brain disorders."

Now that the researchers have shown that the gamma-protocadherin family, as a whole, is critical for dendrite branching, they plan to become more focused in their research. Next, they plan to ask whether specific interactions between individual members of the family are important for instructing neurons on the location and size of dendrite growth.

Source: Science Daily