Project Summary

Jurgen Zschocke, Ph.D. (Young Investigator 2008) of the Max Planck Institute for Psychiatry, seeks to test the hypothesis that modulating epigenetic marks represents a novel means of restoring specific neurotransmitter circuits that have run out of balance. Conventional antidepressants usually target the serotonergic and noradrenergic system, although it is becoming increasingly evident that other neurotransmitter pathways also play an important role in the pathophysiology of these disorders. Dr. Zschocke is interested in an alternative approach, based on a drug-induced improvement of glutamate clearance from the extracellular space, a process accomplished by glutamate transporters (EAAT2). EAAT2 proteins remove glutamate molecules from the synapse through the uptake into neighboring glial cells. Gaining new insights into the molecular modes of EAAT2 regulation -- a goal of this study -- might contribute to the development of new strategies to enhance the function of this crucial transporter. To do so he will employ primary astrocytic cultures and animal models, and analyze a number of different classes of epigenetically acting compounds (e.g. valproate, butyrate, MS-275, 5-AZA) for their impact on the biochemical modification of the EAAT2 gene, levels of gene expression, and protein function.

Program Area: MOOD DISORDERS\Mood Disorders (General)

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