INVESTIGADORES
PODEROSO Juan Jose
artículos
Título:
Progesterone Protective Effects In Neurodegeneration And Neuroinflammation.
Autor/es:
DE NICOLA AF, GONZALEZ-DENISELLE MC, GARAY L, MEYER M, GARGIULO-MONACHELLI G, GUENNOUN R, SCHUMACHER M, 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 antiinflammatory  factor for the nervous system. Here we discuss progesterone effects in models of  motoneuron degeneration and neuroinflammation. In neurodegeneration of the  Wobbler mouse, a subset of spinal cord motoneurons showed increased activity of  nitric oxide synthase (NOS), increased intramitochondrial NOS, decreased activity of  respiratory chain complexes and decreased activity and protein expression of Mnsuperoxide  dismutase type 2 (MnSOD2). Clinically, Wobblers suffered several  degrees of motor impairment. Progesterone treatment restored the expression of  neuronal markers, decreased the activity of NOS and enhanced complex I  respiratory activity and MnSOD2. Long-term treatment with progesterone increased  muscle strength, biceps weight and survival. Collectively, these data supported that  progesterone prevented neurodegeneration. To study progesterone effects in  neuroinflammation, we employed mice with experimental autoimmune  encephalomyelitis (EAE). EAE mice spinal cord showed increased mRNA levels of  the inflammatory mediators tumour necrosis factor α (TNFα) and its receptor TNFR1,  the microglial marker CD11b, iNOS and the toll-like receptor 4 (TLR4). Progesterone  pretreatment of EAE mice blocked the proinflammatory mediators, decreased Iba1+  microglial cells and attenuated clinical signs of EAE. Therefore, reactive glial cells  became targets of progesterone anti-inflammatory effects. These results open the  ground for testing the usefulness of neuroactive steroids for neurological disorders.