Premium
Progesterone Protective Effects in Neurodegeneration and Neuroinflammation
Author(s) -
De Nicola A. F.,
Gonzalez Deniselle M. C.,
Garay L.,
Meyer M.,
GargiuloMonachelli G.,
Guennoun R.,
Schumacher M.,
Carreras M. C.,
Poderoso J. J.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12043
Subject(s) - neuroinflammation , neurodegeneration , endocrinology , neuroprotection , medicine , experimental autoimmune encephalomyelitis , nitric oxide synthase , proinflammatory cytokine , microglia , central nervous system , inflammation , nitric oxide , disease
Progesterone is a neuroprotective, promyelinating and anti‐inflammatory factor for the nervous system. Here, we review the effects of progesterone in models of motoneurone degeneration and neuroinflammation. In neurodegeneration of the W obbler mouse, a subset of spinal cord motoneurones showed increased activity of nitric oxide synthase ( NOS ), increased intramitochondrial NOS , decreased activity of respiratory chain complexes, and decreased activity and protein expression of M n‐superoxide dismutase type 2 ( M n SOD 2). Clinically, W obblers 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 M n SOD 2. Long‐term treatment with progesterone increased muscle strength, biceps weight and survival. Collectively, these data suggest that progesterone prevented neurodegeneration. To study the effects of progesterone 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 ( TNF) α and its receptor TNFR 1, the microglial marker CD 11b, inducible NOS and the toll‐like receptor 4. Progesterone pretreatment of EAE mice blocked the proinflammatory mediators, decreased I ba1+ microglial cells and attenuated clinical signs of EAE . Therefore, reactive glial cells became targets of progesterone anti‐inflammatory effects. These results represent a starting point for testing the usefulness of neuroactive steroids in neurological disorders.