Searching for the Molecular Basis of Major Depressive Disorder (MDD)
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In this video presentation, Dr. Greengard describes his research group's investigation of the molecular and cellular basis of Major Depressive Disorder (MDD) and the mechanism of action of the antidepressant drugs used to treat this disorder.
"We have found that a protein called p11 (S100A10, a member of the S100 family of proteins) plays a central role in the regulation of mood and in the response to antidepressant agents. Constitutive p11 knockout mice manifest a depressive phenotype and exhibit a loss of neurogenic response and behavioral response to antidepressant agents. The depressive phenotype seen in the constitutive p11 knockout mice is attributable to giant cholinergic interneurons in the nucleus accumbens. The loss of behavioral response to antidepressants can be mimicked by deletion of p11 from any of several brain regions. The antidepressant action of p11 and its binding partner, annexin A2, requires the binding of the (p11)2 (annexinA2)2 heterotetramer to a chromatin-remodeling factor, SMARCA3. SMARCA3, in turn, regulates some of the neurogenic and behavioral actions of the antidepressants."