Biomarkers

MIT Researchers Recreate Autism in Mice

Source: 
Medical News Today
Date Published: 
March 20, 2011
Abstract: 

By mutating a single gene, researchers at MIT and Duke have produced mice with two of the most common traits of autism - compulsive, repetitive behavior and avoidance of social interaction. In this study, the researchers focused on one of the most common of those genes, known as shank3. Shank3 is found in synapses - the junctions between brain cells that allow them to communicate with each other. Feng, who joined MIT and the McGovern Institute last year, began studying shank3 a few years ago because he thought that synaptic proteins might contribute to autism and similar brain disorders, such as obsessive compulsive disorder.

Gene Variants in Autism Linked to Brain Development

Source: 
Journal of Molecular Psychiatry, Gai et al.
Date Published: 
March 2011
Year Published: 
2011

This research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling. While an association between genomic variants in certain nervous system processes and autism has been hypothesized in the past, this research definitively links these biological functions to autism. 

"This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both synaptic function and neurotransmission," said senior author Peter S. White, Ph.D., a molecular geneticist and director of the Center for Biomedical Informatics at The Children's Hospital of Philadelphia. Synapses are the contact points at which nerve cells communicate with other nerve cells, while neurotransmitters are the chemical messengers carrying those signals.

"Prior genomic studies of autism have successfully identified several genes that appear to confer risk for autism, but each gene appears to contribute to only a small percentage of cases," said the lead author, Xiaowu Gai, Ph.D. "Our approach considered whether groups of genes with common biological functions collectively accounted for a greater percentage of autism risk."

-- via Science Daily http://www.sciencedaily.com/releases/2011/03/110301111243.htm.

Shank3 Mutant Mice Display Autistic-like Behaviors and Striatal Dysfunction

Source: 
Nature, Peça et al.
Date Published: 
March 2011
Year Published: 
2011

Currently, the neurological basis of autism spectrum disorders (ASDs) is poorly understood. “Shank3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs”. In this study, mice with the Shank3 deletion were seen to exhibit “self-injurious repetitive grooming and deficits in social interaction.” Cellular, electrophysiological, and biochemical analyses revealed defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. The study’s findings demonstrate that Shank3 plays a critical role in the development of neuronal connectivity. The study also established a causality between a disruption in the Shank3 gene and the beginning of autistic-like behaviors in mice.

Researchers Reveal First Autism Candidate Gene That Demonstrates Sensitivity to Sex Hormones

Source: 
Science Daily
Date Published: 
February 17, 2011
Abstract: 

George Washington University researcher, Dr. Valerie Hu, Professor of Biochemistry and Molecular Biology, and her team at the School of Medicine and Health Sciences, have found that male and female sex hormones regulate expression of an important gene in neuronal cell culture through a mechanism that could explain not only higher levels of testosterone observed in some individuals with autism, but also why males have a higher incidence of autism than females.

A Set Of Brain Proteins Is Found To Play A Role In Over 100 Brain Diseases And Provides A New Insight Into Evolution Of Behavior

Source: 
Medical News Today
Date Published: 
December 21, 2010
Abstract: 

In research just published, scientists have studied human brain samples to isolate a set of proteins that accounts for over 130 brain diseases. The paper also shows an intriguing link between diseases and the evolution of the human brain.

Mitochondrial Dysfunction in Autism

Source: 
Journal of the American Medical Association, Giulivi et al
Date Published: 
December 2010
Year Published: 
2010

Children with autism are far more likely to have deficits in their ability to produce cellular energy than are typically developing children. While the study is small (10 test subjects) and requires replication, it furthers previous research which has revealed hints of a mitochondrial dysfunction/autism connection. The researchers found that mitochondria from children with autism consumed less oxygen than mitochondria from the group of control children. For example, the oxygen consumption of one mitochondrial enzyme complex, NADH oxidase, in autistic children was only 33% of that found in control children. While Giulivi cautions that this study has not found the cause of autism, she states that it "...furthers the understanding of autism on several fronts and may, if replicated, be used to help physicians diagnose the problem earlier."

Altered Functional Connectivity in Frontal Lobe Circuits Is Associated with Variation in the Autism Risk Gene CNTNAP2

Source: 
Pediatrics, Scott-Van Zeeland et al
Date Published: 
December 2010
Year Published: 
2010

People with a common variant of the CNTNAP2 gene, a gene associated with a heightened risk of autism, ADD/ADHD and other language difficulties, have a "disconnect" between their frontal lobe and other areas of the brain important for language, according to this fMRI study. The disconnect may help explain some of the language and communication difficulties that are characteristic of autism. About one-third of all people carry the variant of the CNTNAP2 gene.

Regardless of whether the test subjects had autism or not, children with the CNTNAP2 "risk" gene showed more activity in the frontal lobe of the brain during a "language learning" task than those without the 'risk' gene.

Children With Autism Have Mitochondrial Dysfunction, Study Finds

Source: 
Science Daily
Date Published: 
November 30, 2010
Abstract: 

Children with autism are far more likely to have deficits in their ability to produce cellular energy than are typically developing children, a new study by researchers at UC Davis has found. The study, published in the Journal of the American Medical Association (JAMA), found that cumulative damage and oxidative stress in mitochondria, the cell's energy producer, could influence both the onset and severity of autism, suggesting a strong link between autism and mitochondrial defects.

Brain Scans Detect Autism's Signature

Source: 
Science Daily
Date Published: 
November 16, 2010
Abstract: 

An autism study by Yale School of Medicine researchers using functional magnetic resonance imaging (fMRI) has identified a pattern of brain activity that may characterize the genetic vulnerability to developing autism spectrum disorder (ASD).

The team identified three distinct "neural signatures": trait markers -- brain regions with reduced activity in children with ASD and their unaffected siblings; state markers -- brain areas with reduced activity found only in children with autism; and compensatory activity -- enhanced activity seen only in unaffected siblings. The enhanced brain activity may reflect a developmental process by which these children overcome a genetic predisposition to develop ASD.

Inhibitory Neurons Key to Understanding Neuropsychiatric Disorders

Source: 
Science Daily
Date Published: 
November 11, 2010
Abstract: 

In 1999, Baylor College of Medicine researcher Dr. Huda Zoghbi and her colleagues identified mutations in the gene called MECP2 as the culprit in a devastating neurological disorder called Rett syndrome . In new research in mice published in the current issue of the journal Nature, Zoghbi and her colleagues demonstrate that the loss of the protein MeCP2 in a special group of inhibitory nerve cells in the brain reproduces nearly all Rett syndrome features.