Project Summary

Xiaodong Zhang, Ph.D. (Young Investigator 2006) of Duke University Medical Center and Duke University, will study the role of the tryptophan hydroxylase-2 (TPH2) gene, which controls brain serotonin synthesis, in depression. Decreased serotonin levels are believed to play a role in depression. Dr. Zhang plans to use cellular and molecular biology and genetic and animal model studies to characterize neuronal-specific TPH2. Dr. Zhang will generate cell lines expressing wild-type and naturally occurring mutations of human TPH2, and assess their production and regulation of serotonin. He will also examine the role of intronic and exonic polymorphisms in pre-mRNA splicing of TPH2. Moreover, he will perform neurochemical and behavioral tests on mouse strains he is developing that have reduced TPH2 gene expression. In addition, chronic antidepressant treatment of these mice with varying brain serotonin levels may provide clues about resistance to or adverse effects of antidepressant treatment. Results will provide insights about the regulation of TPH2 in brain serotonin synthesis, and potential new targets for treatments.

Program Area: MOOD DISORDERS

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