Project Summary

Dwight E. Bergles, Ph.D. (Young Investigator 2005) of Johns Hopkins University, plans to study how oligodendrocyte precursor cells may play a role in schizophrenia and depression. Oligodendrocytes are glial cells that produce myelin, a type of insulation around axons that allows electrical signals to be transmitted rapidly over long distances. Recent studies indicate that schizophrenic patients exhibit a decrease in myelin in the prefrontal cortex, a decrease in expression of myelin-associated genes, and a decrease in oligodendrocyte density, suggesting that death or dysfunction of these cells may contribute to the behavioral changes seen in this disease. Oligodendrocytes are generated throughout life from progenitor cells, termed oligodendrocyte precursor cells (OPCs). The dearth of oligodendrocytes in schizophrenia suggests that OPC differentiation may be interrupted. Dr. Bergles’s laboratory discovered that OPCs in the hippocampus express receptors for the glutamate and GABA neurotransmitters and engage in rapid communication with surrounding neurons through direct synapses. Glutamate receptor activation inhibits the differentiation of OPCs in vitro, suggesting that abnormal neuron-OPC signaling at synapses may contribute to oligodendrocyte dysfunction in schizophrenia and major depression. Other recent studies have shown that antidepressive therapies increase OPC proliferation, while stress decreases OPC proliferation. Dr. Bergles proposes to examine the properties of OPCs in the amygdala and prefrontal cortex, determine whether these cells form synapses with neurons, and evaluate whether antidepressive therapy (electroconvulsive shock, fluoxetine treatment) or glucocorticoids alter signaling at these neuron-OPC synapses. These studies of neuron-glia signaling may provide new insights into the mechanisms responsible for the beneficial effects of antidepressive therapy.

Program Area: MULTIPLE FOCUS AREAS\Unipolar/Schizophrenia

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