New Evidence that a Faulty Gene Impairs Nerve Cell Communication in Autism

New Evidence that a Faulty Gene Impairs Nerve Cell Communication in Autism

Posted: October 30, 2015

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Researchers studying people diagnosed with autism spectrum disorders (ASD) have uncovered rare mutations in a gene involved in brain cell communication.  As they report online September 15 in Molecular Psychiatry, the mutations in the GLRA2 gene seem to stunt the growth of certain neural connections, leading to ASD and learning and memory problems in mice.

The GLRA2 gene encodes a cell receptor, an important communication port for cell-to-cell signaling by a neurotransmitter called glycine. The team of researchers, led by Catalina Betancur, M.D., Ph.D., of INSERM in France, said their findings link glycine signaling to some of the cognitive deficits found in disorders such as ASD.

The GLRA2 gene is located on the X chromosome, of which males have one copy and females two copies. Like in other X chromosome-linked disorders, this could explain why GLRA2 alterations only affect males, since they lack a second X chromosome to compensate for any GLRA2 mutation. Dr. Betancur, a 2010 NARSAD Independent Investigator, was joined on the study by INSERM and Douglas Mental Health University Institute researcher Bruno Giros, Ph.D., a 1992 recipient of the NARSAD Young Investigator grant.

Experiments by Dr. Betancur and colleagues show that the mutations identified in GLRA2 weaken the cell’s ability to respond to glycine. In experiments with zebrafish, the scientists showed that inactivation of the gene led to severe defects in the growth of nerve cell communication branches called axons.

Mice that lack the GLRA2 gene are similar to normal mice in their social interactions and levels of anxiety, Dr. Betancur and colleagues concluded in further experiments. However, mice missing GLRA2 perform worse than normal mice on tests of short and long-term memory and show changes in the strength of the synapses, or signaling connections, between brain cells.

The scientists believe that disruptions of the GLRA2 gene are likely to cause an imbalance between excitatory and inhibitory neurotransmission, the mechanisms devoted to shutting down and revving up communication in the brain’s neural networks. This type of imbalance may play a role in the development of ASD and other similar neurodevelopment disorders such as epilepsy and schizophrenia, the researchers note.

Read the abstract.

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