Therapeutic Effects of Progesterone in Animal Models of Neurological Disorders

DE NICOLA A; CORONEL F; GARAY, L; GARGIULO G; GONZÁLEZ DENISELLE MC; GONZÁLEZ SL; LABOMBARDA, F; MAYER M; GUENNOUN R; SCHUMACHER M

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2013 vol. 12 p. 1205 - 1208

1871-5273

Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervoussystem unrelated to its classical role in reproduction. In this review we first discussed progesterone effects followingbinding to the classical intracellular progesterone receptors A and B and several forms of membrane progesteronereceptors, the modulation of intracellular signalling cascades and the interaction of progesterone reduced metabolites withneurotransmitter receptors. We next described our results involving animal models of human neuropathologies toelucidate the protective roles of progesterone. We described: (a) the protective and promyelinating effects of progesteronein experimental spinal cord injury, (b) the progesterone protective effects exerted upon motoneurons in the degeneratingspinal cord of Wobbler mouse model of amyotropic lateral sclerosis; (c) the protective and anti-inflammatory effects ofprogesterone in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis and after lysolecithindemyelination; (d) the progesterone prevention of nociception and neuropathic pain which follow spinal cord injury, and(e) the protective effect of progesterone in experimental ischemic stroke. Whenever available, the molecular mechanismsinvolved in these progesterone effects were examined. The multiplicity of progesterone beneficial effects has opened newvenues of research for neurological disorders. In this way, results obtained in animal models could provide the basis fornovel therapeutic strategies and pre-clinical studies.