Project Summary

Meng-Yang Zhu, M.D., Ph.D. (Young Investigator 2006) of the University of Mississippi Medical Center, will study the role of two transcription factors, Phox2a and Phox2b, on the noradrenergic system and hippocampal neurogenesis, both of which are impaired in major depression. Dr. Zhu’s previous findings show that Phox2a- and Phox2b-expression in the rat locus coeruleus (LC) are related to dopamine p-hydroxylase (DBH) and norepinephrine transporter (NET) expression with advanced age. As both DBH and NET are key factors of the noradrenergic system, these results suggest a regulatory effect of Phox2a/2b on the mature noradrenergic system. Utilizing gene transfer and small interfering RNA (siRNA), Dr. Zhu will address: (1) whether overexpression or silencing of Phox2a/2b genes will increase or reduce DBH- and NET-expression in cultured LC neurons, and (2) whetheroverexpression or silencing of Phox2a/2b in the rat LC will change neuroplasticity in the hippocampal dentate gyrus, an LC neuronal terminal area in the rat brain. Findings should elucidate the regulation of central noradrenergic neurons by transcription factors and may open new targets for antidepressant therapies.

Program Area: MOOD DISORDERS\Unipolar

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