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Progesterone Protective Effects in Neurodegeneration and Neuroinflammation
- Source :
- CONICET Digital (CONICET), Consejo Nacional de Investigaciones Científicas y Técnicas, instacron:CONICET
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- 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
- Subjects :
- medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
Encephalomyelitis, Autoimmune, Experimental
Neuroactive steroid
Endocrinology, Diabetes and Metabolism
Neurociencias
Respiratory chain
Biology
Neuroprotection
Proinflammatory cytokine
Mice
Cellular and Molecular Neuroscience
Endocrinology
Internal medicine
medicine
Animals
Progesterone
Neuroinflammation
NEUROPROTECTION
Endocrine and Autonomic Systems
WOBBLER MOUSE
Neurodegeneration
Experimental autoimmune encephalomyelitis
Neurodegenerative Diseases
PROGESTERONE
purl.org/becyt/ford/3.1 [https]
medicine.disease
ANTI-INFLAMMATORY EFFECTS
Nitric oxide synthase
Medicina Básica
Disease Models, Animal
Neuroprotective Agents
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
biology.protein
purl.org/becyt/ford/3 [https]
Progestins
Subjects
Details
- ISSN :
- 09538194
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroendocrinology
- Accession number :
- edsair.doi.dedup.....36bc419ec0039c6920140ed28207473c