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Identification and Microassay of Neuroactive Steroids : Physiological and Pathophysiological Significance

Objective

To set up a centralized facility in Europe for the microassay of steroids by gas-chromatography-mass fragmentography (GC-MF), operating the MF in the negative ion chemical detection (NICI) mode.
To compare individual characteristics and performances with the concentrations of relevant steroids in defined nervous structures, and thus to establish the physiological and pathophysiological role of neurosteroids in nervous system functioning.

The specific aim of this proposal is to measure neurosteroids in both CNS and PNS, under normal and pathological conditions and after injury by GC-MF. The steroids to be measured are those with documented neuroactive properties : either steroid hormones involved in genomic regulation (progesterone, 5a-dihydroprogesterone, deoxycorticosterone, corticosterone or cortisol, testosterone and 5a-dihydrotestosterone), or steroids endowed with neuromodulatory properties (allopregnanolone, tetrahydrodeoxycorticosterone, pregnenolone sulfate, dehydroepiandrosterone sulfate). A complete validation of this new method as applied to neurosteroids will be needed.
Steroid assays will also be performed in cell culture and coculture media and will be completed by biochemical and biological molecular investigations of the enzymes involved in their biosynthesis and metabolism.
Interest will focus on the in vitro and in vivo trophic effects of neurosteroids, as involved in nerve regeneration and myelin repair, and on the behavioural effects of neurosteroids, particularly on ageing related memory disturbances.

Funding Scheme

CON - Coordination of research actions

Coordinator

Institut National de la Santé et de la Recherche Médicale
Address
80,Rue Du General Leclerc
94276 Kremlin-bicetre
France