Project Summary

Laurent Givalois, Ph.D. (Independent Investigator 2002) of University of Montpellier II, is examining the most prominent and well-documented neuroendocrine abnormality of depression, characterized by an hippocampo-hypothalamo-pituitary adrenocortical (HHPA) axis hyperactivity.  All treatments, including “electro-convulsive therapy” might boost the production of endogenous factors, named neurotrophins.  Neurotrophins, and more particularly brain-derived neurotrophic factor (BDNF), promote the function and growth of serotonin neurons in the adult brain and increase the turnover of serotonin and norepinephrine levels in many forebrain areas, suggesting that neurotrophins could be possible mediators in depression.  Also, stress is often considered as a trigger factor in depression and responsible for the HHPA axis activation, has been shown to decrease BDNF mRNA in adult brain.  Another family of molecules, named neurosteroids could interact with neurotrophins to counteract the effects of depression.  The relationship between depression and neurosteroids is intriguing, and much work needs to be done.  The aim of this study is to determine if BDNF could interact with neurosteroids (DHEA/DHEA-S) to counteract some central noxious effects found in major depression, especially those related to the HPA axis, in an animal model of depression induced by restraint chronic stress.  Its development could help us to understand the role of neurotrophic factors and its possible interaction with neurosteroids in depressive disorder consecutive to chronic stress and thus opening new research insights on therapy strategies.

Program Area: MOOD DISORDERS\Depression (Unipolar)

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