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[February 21, 2017]

Drugs that Alter Inhibitory Targets Offer Therapeutic Strategies for Autism, Schizophrenia

Targeted Drug Therapies during Adolescence May Be Used to Normalize Synapse Number in the Brains of Individuals with Abnormal Numbers of Synapses, Such As Found in Schizophrenia and Autism

 

Brooklyn, NY – Memories are formed at structures in the brain known as dendritic spines, which communicate with other brain cells through “synapses.” The number of these brain connections decreases by half after puberty in a process termed adolescent “synaptic pruning” that is necessary for normal learning in adulthood. However, the pruning away of unnecessary synapses does not follow the normal process in diseases such as autism and schizophrenia, where the abnormality is thought to underlie many of the cognitive impairments associated with these disorders.

Researchers at SUNY Downstate Medical Center recently discovered that an inhibitory brain receptor triggers pruning in adolescence in a pre-clinical model. Now, a new article by the SUNY Downstate researchers shows that drugs that selectively target these receptors, when administered during adolescence, can alter synapse number.

Sheryl S. Smith, PhD, professor of physiology and pharmacology at Downstate, explains, “Drugs that enhance activity of this inhibitory receptor reduce synapse number, while drugs that decrease this inhibitory receptor increase synapse number.”

Dr. Smith adds, “These findings suggest that targeted drug therapies during adolescence could potentially be used to normalize synapse number in the brains of individuals with abnormal numbers of synapses, such as found in autism and schizophrenia.” Dr. Smith cautions, however, that at this time such drugs are not yet available for use in humans.

The article is "α4βδ GABAA receptors reduce dendritic spine density in CA1 hippocampus and impair relearning ability of adolescent female mice: Effects of a GABA agonist and a stress steroid," by Sonia Afroz, Hui Shen, Sheryl S. Smith (http://dx.doi.org/10.1016/j.neuroscience.2017.01.051). It appears in Neuroscience, Volume 347 (April 2017), published by Elsevier.
 
The research leading to the results published by Neuroscience was supported by the National Institutes of Health/National Institute of Mental Health, Award Number R01-MH100561, to Sheryl S. Smith. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or National Institutes of Health.
Copies of this paper are available to credentialed journalists upon request; please contact Elsevier's Newsroom at newsroom@elsevier.com or +31 20 485 2492.

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About SUNY Downstate
SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient’s bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, College of Nursing, College of Health Related Professions, a School of Graduate Studies, a School of Public Health, University Hospital of Brooklyn, and a multifaceted biotechnology initiative including the Downstate Biotechnology Incubator and BioBAT for early-stage and more mature companies, respectively. SUNY Downstate ranks twelfth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school. For more information, visit www.downstate.edu.

About Neuroscience
An International Journal under the editorial direction of IBRO, Neurosciencepublishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.
   

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