Progesterone protective effects in neurodegeneration and neuroinflamation

Authors
de Nicola, Alejandro Federico; Gonzalez Deniselle, Maria Claudia; Garay, Laura Ines; Meyer, Maria; Gargiulo Monachelli, Gisella Mariana; Guennoun, Rachida; Schumacher, M.; Carreras, Maria Cecilia; Poderoso, Juan José
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
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.
Fil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Garay, Laura Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Meyer, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Gargiulo Monachelli, Gisella Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Guennoun, Rachida. Inserm; Francia. Universite Paris Sud; Francia
Fil: Schumacher, M.. Inserm; Francia. Universite Paris Sud; Francia
Fil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina
Subject
PROGESTERONE
NEUROPROTECTION
WOBBLER MOUSE
ANTI-INFLAMMATORY EFFECTS
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
Neurociencias
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/5535