Project Summary

Haim Einat, Ph.D. (Young Investigator 2005) of the National Institute of Mental Health, proposes studying in mice the role the protein BCL-2 might play in bipolar disorder. Some recent evidence suggests that BCL-2 may be implicated in bipolar disease: BCL-2 proteins are involved in regulating synaptic plasticity and neuronal survival. BPD is associated with impairments of synaptic plasticity and cellular resilience. And the mood stabilizers lithium and valproate robustly activate BCL-2 in vitro and in vivo. Now, Dr. Einat would like to determine if manipulating BCL-2 levels in mice will result in affective-like behavioral changes and whether these changes are sensitive to mood stabilizer treatment. He plans to examine the behavior of mutant mice that overexpress or underexpress the BCL-2 gene (therefore showing increased or decreased BCL-2 protein levels) when given and not given mood stabilizers. Manic and depressed behavior will be measured using standard mouse assays that monitor activity levels, novelty exploration, risk-taking behavior, hedonism, despair, withdrawal and aggression. Findings could reveal the link between BCL-2 and behavior, and may lead to novel treatments that target molecules involved in critical CNS cell survival.

Program Area: MOOD DISORDERS\Bipolar

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