UNDERGRADUATE SUMMER RESEARCH PROGRAM
2010 NSSP Information
Beata Karolewicz, Ph.D.
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Beata Karolewicz, Ph.D. CPN Project Principal Investigator Assistant Professor Department of Psychiatry and Human Behavior Contact Dr. Karolewicz Co-Investigators: TBA |
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Key Laboratory Personnel:
Laurel Johnson, Research Tech
"Glutamate System in Depression"
A large amount of research provides compelling supportive evidence for a dysfunction in the brain's glutamate signaling system in major depressive disorder (MDD). This postulate is based on 1) evidence of increased levels of glutamate in vivo in the brain of depressed patients; 2) postmortem evidence of altered levels of proteins related to glutamate transmission; 3) antidepressant-like potential of agents decreasing glutamate signaling in rodents and humans. Our preliminary investigations using postmortem human brain tissue have provided evidence of abnormalities in indices of glutamatergic signaling in the brainstem from subjects with MDD. In conjunction with research by other laboratories, our preliminary findings have demonstrated that abnormal glutamatergic neuronal activity in MDD can be revealed by neurochemical abnormalities in the postmortem brain. An area of the brain where glutamate is a critical component of neuronal circuitry and where gross neuropathology has been reproducibly demonstrated in MDD is the hippocampus. Reductions in hippocampal volume and neuropil have been reported for MDD subjects. Interestingly, in laboratory animals, brain glutamate levels are increased after exposure to stress and chronic stress produces hippocampal atrophy. Based on these findings and our preliminary data, we hypothesize that at least part of the pathology of the hippocampus in MDD is triggered by elevated glutamate signaling. This elevated signaling will be revealed by abnormalities in glutamate indices, such as glutamate transporters, receptors and their intracellular-associated molecules, in the hippocampus. To achieve these goals postmortem brain tissues from MDD subjects and carefully matched psychiatrically normal controls will be utilized. Diagnoses are made via a rigorous psychiatric autopsy program under the direction of Dr. Craig Stockmeier. Overall, the proposed research will elucidate the molecular underpinning of glutamate pathology and may yield new targets for novel therapeutic approaches to treatment of depressive disorders.