Project Summary

Houhui Xia, Ph.D. (Young Investigator 2004) of Louisiana State University Health Sciences Center, proposes studying the mechanisms underlying neuronal plasticity that go awry in depression. In the project, Dr. Xia will focus on mechanisms by which plasticity is achieved through enhancing the expression of genes mediated by a key gene transcription factor, CREB. Recent evidence suggests that class-I histone deacetylase (HDAC) is critical in this process. Dr. Xia plans to study whether HDAC functions by (a) targeting Protein Phosphatase-1 (PPI) to dephosphorylate CREB, thus decreasing its activity; and simultaneously (b) keeping DNA in a condensed state not supportive of gene transcription. He will determine the effect of blocking PPI targeting and mutating HDAC's "DNA condensing" function on CREB-mediated gene transcription in dissociate-cultured hippocampal neurons. His laboratory will also test the effect of the anti-depressant drug valproic acid on CREB-mediated gene transcription. He also will test CREB activation and inhibition in an animal model of depression.

Program Area: MOOD DISORDERS\Unipolar Depression

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