Zhe-Yu Chen, M.D., Ph.D. (Young Investigator 2005) of Weill Medical College of Cornell University, plans to characterize how a newly identified human mutation in the brain-derived neurotrophic factor (BDNF) gene leads to altered nervous system function, and, thus, may contribute to psychiatric disease. BDNF plays a critical role in the in nervous system and has been implicated antidepressant and mood stabilizer action and the pathophysiology of affective disorders. Recently, a single nucleotide change in the BDNF gene, (BDNFmet), was found to increase susceptibility to neuropsychiatric disorders, such as depression, bipolar disorder, obsessive compulsive disorder, and altered episodic memory. Dr. Chen hypothesizes that the BDNF alteration results in defective intracellular BDNF trafficking in the highly specialized regulatory secretion pathway present in neural cells, and leads to altered nervous system function. Dr. Chen proposes to test the hypothesis by identifying the intracellular and extracellular fates of variant BDNF in neuronal cells obtained from a BDNFmet knock-in mouse, and by analyzing the in vivo consequences of the variant BDNF through the use of neuronal morphological, electrophysiological, and behavioral assays. Findings should advance understanding of BDNF’s role in the pathophysiology of a variety of neuropsychiatric disorders affecting mood and higher cognitive abilities.
Program Area: MOOD DISORDERS\Mood Disorders (General)
