Project Summary

Leonard L. Jones, Ph.D. (Young Investigator 2004) of University of California, San Diego, aims to test whether a targeted decrease of expression of brain-derived neuronal growth factor (BDNF) in the rat brain induces behavioral effects similar to other animal models of neuropsychiatric disorders. BDNF has been implicated in bipolar disorder and is reduced in patients with major depression and schizophrenia. In the proposed study, Dr. Jones will silence gene expression in specific rat brain regions and monitor the behavioral result. He will create in a lentivirus vector small interfering RNAs (siRNA) that target and degrade BDNF mRNA. Effective lentivirus-based siRNAs will then be introduced for long-term, genomic expression of siRNA specific to BDNF to downregulate the expression of this neurotrophic factor in the rat brain. Behavioral testing will evaluate locomotion, vertical movements, eating, drinking and other activities. If BDNF expression is successfully decreased and certain behavioral effects are observed, subsequent studies could analyze other genes involved in this pathway.

Program Area: MULTIPLE FOCUS AREAS\Mood Disorders/Schizophrenia

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