If carbon dioxide emissions continue unabated, expanding oceans and massive ice melt would threaten global coastal communities, according to new projections.
Anti-anxiety drug clonazepam reduces autistic features in mouse model of Jacobsen syndrome.
Discovered only in the 1990s, microRNAs are short molecules that work within virtually all cells.
Depression is epidemic in our society, and the mainstream solution is a trip to the psychiatrist and an indefinite prescription for pharmaceuticals. Dependent…
Discoveries about how the human brain contributes to our success – both as a species and as individuals – are among the first fruit of projects funded under the National Institutes of Health BRAIN Initiative program as well as the Human Connectome Project. One study may help to explain the mystery of how our primate brain’s outer mantle, or cortex, was able to expand as much as 1000-fold through evolution, compared to other mammals. The other reveals that the more successful we tend to be – score higher on commonly considered positive personal qualities, such as education and income levels and life satisfaction – the more key parts of our brain tend to talk with each other when we’re not doing anything in particular.
A team of BRAIN Initiative-supported scientists, led by Arnold Kriegstein of University of California, San Francisco, reported
in Cell, Sept. 24, 2015, on what may be the secret to the human cortex’s exponential growth. Another team led by Stephen Smith of University of Oxford, UK, and David Van Essen, Washington University, St. Louis, explains findings linking brain connectivity to measures of personal success Sept. 28, 2015 in the journal Nature Neuroscience. The studies were funded, in part, by the National Institute of Mental Health (NIMH) and other NIH components.
Kriegstein and colleagues found that the human cortex harbors a unique support system for neuron-producing factories during early brain development — in outlying cellular neighborhoods that barely exist in lower animals. The researchers discovered the molecular underpinnings of this unique group of stem cells that churn out thousands of neurons and support cells where their mouse counterparts produce only 10-100. They also discovered that the secret to this prolific output seems to lie in these cells’ ability to carry with them their own self-renewing ” niches,” – support systems that enabled them to thrive in far flung circuit suburbs. The results add to s deeper understanding of the human brain’s parts list and enhance scientists’ ability to perform disease-in-a-dish experiments relevant to uniquely human disorders like autism and schizophrenia, which are difficult to model in rodents.
Smith’s group mined Human Connectome Project data on 461 individuals to find out whether any patterns of brain connectivity are associated with specific sets of correlated demographics and behavior. In addition to images of their resting state structural and functional brain connections, the Project collected data on 280 such subject measures, including psychological factors such as IQ, language performance, rule-breaking behavior and anger. A set of such measures statistically related to each other emerged as strongly correlated with connectivity between certain brain structures prone to talking with each other during the brain’s default mode, or resting state. This set was mostly composed of positive personal qualities, such as high performance on memory and thinking tasks, life satisfaction, years of education, and income. The set turned out to have a more than three-fold stronger correlation with increased brain connectivity than any of 99 other sets of measures examined. The brain regions associated with the set, which may be related to general intelligence, have been linked to higher-level human thinking – e.g., memory, imagination, sociability, value-guided decision-making and reasoning.
“It may be expected that these aspects of cognitive function would have an influence on life in a complex society,” note Smith and colleagues.
“It is great to see data from large investments like the Human Connectome Project and the BRAIN Initiative result in such interesting science so quickly,” said Greg Farber, Ph.D., director of NIMH’s Office of Technology Development and Coordination. “Both efforts seem very well positioned to continue to provide the research community with new tools and results to enhance our understanding of the brain.”
Adapted by MNT from original media release
Molecular Identity of Human Outer Radial Glia during Cortical Development. Pollen AA, Nowakowski TJ, Chen J, Retallack H, Sandoval-Espinosa C, Nicholas CR, Shuga J, Liu SJ, Oldham MC, Diaz A, Lim DA, Leyrat AA, West JA, Kriegstein AR. Cell. 2015 Sep 24;163(1):55-67. doi: 10.1016/j.cell.2015.09.004. PMID: 26406371
A positive-negative mode of population covariation links brain connectivity, demographics and behavior. Smith SM, Nichols TE, Vidaurre D, Winkler AM, Behrens TEJ, Glasser MF, Ugurbil K, Barch DM, Van Essen DC, Miller Kl. Nature Neuroscience, September 28, 2015.
By identifying a key signaling defect within a specific membrane structure in all cells, University of California, Irvine researchers believe, they have found both a possible reliable biomarker for diagnosing certain forms of autism and a potential therapeutic target.
Dr. J. Jay Gargus, Ian Parker and colleagues at the UCI Center for Autism Research & Translation examined skin biopsies of patients with three very different genetic types of the disorder (fragile X syndrome and tuberous sclerosis 1 and 2). They discovered that a cellular calcium signaling process involving the inositol trisphosphate receptor was very much altered.
This IP3R functional defect was located in the endoplasmic reticulum, which is among the specialized membrane compartments in cells called organelles, and may underpin cognitive impairments – and possibly digestive and immune problems – associated with autism.
“We believe this finding will be another arrow in the quiver for early and accurate diagnoses of autism spectrum disorders,” said Gargus, director of the Center for Autism Research & Translation and professor of pediatrics and physiology & biophysics. “Equally exciting, it also presents a target of a molecular class already well-established to be useful for drug discovery.”
Study results appear online in Translational Psychiatry, a Nature publication, “Shared functional defect in IP3R-mediated calcium signaling in diverse monogenic autism syndromes” doi:10.1038/tp.2015.123 (open access).
Autism spectrum disorder is a range of complex neurodevelopmental disorders affecting 2 percent of U.S. children. The social and economic burden of ASD is enormous, currently estimated at more than $66 billion per year in the U.S. alone. Drug development has proven problematic due to the limited understanding of the underlying causes of ASD, as demonstrated by the recent failure of several much anticipated drug trials.
There are also no current, reliable diagnostic biomarkers for ASD. Genetic research has identified hundreds of genes that are involved, which impedes diagnosis and, ultimately, drug development. There simply may be too many targets, each with too small an effect.
Many of these genes associated with ASD, however, have been found to be part of the same signaling pathway, and multiple defects in this pathway may converge to produce a large functional change.
The UCI scientists detected such a convergence in the IP3R calcium channel in an organelle called the endoplasmic reticulum. Organelles are membrane structures within cells with specialized cellular functions. According to Gargus, diseases of the organelles, such as the ER, are an emerging field in medicine, with several well-recognized neurological ailments linked to two other ones, the mitochondria and lysosomes.
The IP3R controls the release of calcium from the ER. In the brain, calcium is used to communicate information within and between neurons, and it activates a host of other cell functions, including ones regulating learning and memory, neuronal excitability and neurotransmitter release – areas known to be dysfunctional in ASD.
“We propose that the proper function of this channel and its signaling pathway is critical for normal performance of neurons and that this signaling pathway represents a key ‘hub’ in the pathogenesis of ASD,” said Parker, a fellow of London’s Royal Society and UCI professor of neurobiology & behavior, who studies cellular calcium signaling.
To see if IP3R function is altered across the autism spectrum, clinical researchers at the Center for Autism & Neurodevelopmental Disorders – which is affiliated with the Center for Autism Research & Translation – are currently expanding the study and have begun to examine children with and without typical ASD for the same signaling abnormalities. These patients undergo complete behavioral diagnostic testing, and sophisticated EEG, sleep and biochemical studies are performed. This includes the sequencing of their entire genome. Also, skin cell samples are cultured and made available to lab-based researchers for functional assays.
In the area of drug discovery, scientists at the Center for Autism Research & Translation continue to probe the IP3R channel, specifically how it regulates the level of neuron excitability. The brains of people who have autism show signs of hyperexcitability, which is also seen in epilepsy, a disorder increasingly found to be associated with ASD. Cells from individuals who have autism exhibit depressed levels of calcium signaling, and this might explain why these patients experience this hyperexcitability. By restoring the release of calcium from the IP3R, the researchers believe, they can apply a “brake” on this activity.
Adapted by MNT from original media release
Galina Schmunk, Bryan Boubion and Ian Smith of UCI contributed to the study, which received support from the National Institutes of Health (grants GM048071 and GM1000201) and the William & Nancy Thompson Family Foundation. The discovery is being patented by the University of California as a diagnostic tool and for identifying potential therapeutic agents.
University of California – Irvine …………………’
University of California, Irvine researchers with the School of Medicine have identified the mechanism by which valproic acid controls epileptic seizures, and by doing so, also revealed an underlying factor of seizures.
Valproic acid is widely used to treat various types of seizure disorders, but to this point, the cellular mechanism affected by its anticonvulsant properties were not well understood.
Dr. Naoto Hoshi, an associate professor of pharmacology and physiology & biophysics, and colleagues discovered that valproic acid preserved the M-current during seizures. The M-current is mediated through cellular potassium channels and is important for the proper firing of neuronal signals.
The UCI team also uncovered that during seizures, the M-current is suppressed, which contributes to neuronal hyperexcitability. This underlying factor, Hoshi said, contributes to our understanding of seizures and points to the creation of new, more effective drugs that carry fewer side effects.
Valproic acid is also used to treat manic episodes related to bipolar disorder (manic depression) and to prevent migraine headaches, but the drug is linked to liver damage, birth defects and psychiatric side-effects.
Adapted by MNT from original media release
Hee Yeon Kay, Derek Green, Seungwoo Kang and Anastasia Kosenko with UCI contributed to study, which appears in the Journal of Clinical Investigation. The National Institute of Neurological Disorders and Stroke (grant R01 NS067288) supported the research.