Project Summary

Xiao-Ming Ou, Ph.D. (Young Investigator 2002) of University of Southern California, hypothesizes that the abnormal transcriptional regulation of the 5-HT1A receptor by agonists or transcriptional factors may underlie mental illnesses such as depression, anxiety, etc., for which these compounds are effective.  Chronic treatment with various antidepressants down-regulates inhibitory 5-HT1A autoreceptors on serotonergic raphe neurons leading to enhanced serotonergic neurotransmission.  She has identified a 31-bp repressor element in the rat 5-HT1A receptor promoter.  Using this 31-bp element to screen a mouse brain cDNA library, she isolated a cDNA coding a novel protein (Freud-1) that binds to this element.  Dr. Ou hopes to characterize the Freud-1 protein, identify the regulatory mechanisms for the interaction between Freud-1 and DNA, detect the function of Freud-1 in vivo, and isolate other repressor protein(s) or cofactor(s) that interact with Freud-1.  By identifying the transcriptional mechanisms of 5-HT1A, novel targets for the treatment of mental illnesses will be elucidated.

Program Area: MULTIPLE FOCUS AREAS\Mood Disorders/Anxiety Disorders

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