INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
artículos
Título:
Progesterone protective effects in neurodegeneration and neuroinflamation
Autor/es:
A. F. DE NICOLA; M.C. GONZÁLEZ DENISELLE; L. GARAY; M. MEYER; G. GARGIULO-MONACHELLI; R. GUENNOUN; M. SCHUMACHER; CARRERAS MC; PODEROSO JJ
Revista:
JOURNAL OF NEUROENDOCRINOLOGY.
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2013 vol. 25 p. 1095 - 1103
ISSN:
0953-8194
Resumen:
Progesterone is a neuroprotective, promyelinating and anti-inflammatory factor for the nervoussystem. Here, we review the effects of progesterone in models of motoneurone degenerationand neuroinflammation. In neurodegeneration of the Wobbler mouse, a subset of spinal cordmotoneurones showed increased activity of nitric oxide synthase (NOS), increased intramitochondrialNOS, decreased activity of respiratory chain complexes, and decreased activity andprotein expression of Mn-superoxide dismutase type 2 (MnSOD2). Clinically, Wobblers sufferedseveral degrees of motor impairment. Progesterone treatment restored the expression of neuronalmarkers, decreased the activity of NOS and enhanced complex I respiratory activity andMnSOD2. Long-term treatment with progesterone increased muscle strength, biceps weight andsurvival. Collectively, these data suggest that progesterone prevented neurodegeneration. Tostudy the effects of progesterone in neuroinflammation, we employed mice with experimentalautoimmune encephalomyelitis (EAE). EAE mice spinal cord showed increased mRNA levels ofthe inflammatory mediators tumour necrosis factor (TNF)a and its receptor TNFR1, the microglialmarker CD11b, inducible NOS and the toll-like receptor 4. Progesterone pretreatment of EAEmice blocked the proinflammatory mediators, decreased Iba1+ microglial cells and attenuatedclinical signs of EAE. Therefore, reactive glial cells became targets of progesterone anti-inflammatoryeffects. These results represent a starting point for testing the usefulness of neuroactivesteroids in neurological disorders.