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Weill Cornell researchers find that a single gene is responsible for OCD-like behaviors in mice
Date:4/26/2010

s a lot. The researchers videotaped this behavior and quantified it, and found that the knockout mice groomed themselves significantly more than did wild-type mice, which served as the experimental control. A set of follow-up experiments with scientists from Dr. Lee's laboratory, Dr. Kevin Bath and Iva Dincheva, concluded that the mice were also considerably more anxious compared with control mice.

The scientists gave Prozac, a standard drug used in the treatment for patients with OCD, to both sets of mice, and found that excessive grooming stopped completely in the experimental animals. "Now that we have this mouse model, we can test new therapies for OCD that can ultimately be applied to humans," says Dr. Hormigo. "We know Prozac works to ameliorate some OCD symptoms in humans -- the drug also worked for our OCD mice -- but the effect can be temporary and more targeted treatments are needed."

The researchers then looked at brain function in the mice. By examining activity of the reporter gene that was substituted for Slitrk5 in knockout mice, they found that the gene was active throughout the brain, but excessively active in one part of the frontal cortex. Dr. Francis Lee's group, which included co-lead authors Dr. Deqiang Jing and Catia Proenca, then performed sophisticated analyses and discovered structural abnormalities in a related brain region, the striatum, an area of the brain involved in reward and decision-making. Neurons within the striatum were less complex than in normal brain tissue, which is an issue because these neurons act like a hub that receives and transmits input to and from the cortex, says Dr. Jing. Further investigation demonstrated that the level of glutamate receptors in these particular neurons was decreased, compared with control mice. "These molecular findings suggest that this gene plays a unique, unexpected role in modifying glutamate neurotransmission in this particular circuit," says Ms. Proenca.

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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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