Project Summary

Meenakshi Alreja, Ph.D. (Independent Investigator 2001) of Yale University School of Medicine, notes that chronic stress plays an important role in the etiology of mood disorders and a risk factor for neurodegenerative disorders such as Alzheimer's. This study has implications for treatment of cognitive deficits associated mood disorders and neurodegenerative disorders. Hippocampal volume is reduced in patients with stress related psychiatric illnesses, including depression and post traumatic stress disorder. Stress decreases the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, an effect that can reversed by a variety of antidepressant treatments including electroconvulsive shock therapy, but not by non-depressant psychotropic medications. Hippocampal BDNF provides essential trophic support to the cholinergic neurons of the medical septum/diagnosed band region which in turn provide the hippocampus with nearly its entire acetylcholine. Dr. Alreja hypothesizes a loss of hippocampal BDNF, by reducing trophic support to the septohippocampal cholinergic neurons, may comprise cholinergic functions in the septohippocampal pathway and lead to cognitive deficits. She will investigate the status of cholinergic and GABAergic functions in the septohippocampal pathway in BDNF knockout mice and/or mice subjected to stressful conditions and test if antidepressant treatment will reverse the observed changes.

Program Area: MULTIPLE FOCUS AREAS\Alzheimer's/Mood Disorders

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