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Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects
- Source :
- CONICET Digital (CONICET), Consejo Nacional de Investigaciones Científicas y Técnicas, instacron:CONICET
- Publication Year :
- 2018
- Publisher :
- Wiley Blackwell Publishing, Inc, 2018.
-
Abstract
- Progesterone shows anti-inflammatory and promyelinating effects in mice with experimental autoimmune encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Because neurosteroids have been implicated as protective factors for MS and EAE, we analysed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice, which were then killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3β-hydroxysteroid dehydrogenase (3β-HSD) were not significant. mRNA translocator protein (18 kDa) (TSPO) was elevated, concomitantly with a reactive microgliosis. EAE mice also showed abnormal mitochondrial ultrastructure in axons and neuronal bodies, as well as reduced expression of fission and fusion protein mRNAs. Progesterone pretreatment before EAE induction increased Star, VDAC, P450scc, 5α-reductase type I, 3α-HSOR and aromatase mRNAs and did not modify 3β-HSD. TSPO mRNA was decreased, possibly as a result of reversal of microgliosis. Progesterone pretreatment also improved mitochondrial ultrastructure and increased fission/fusion protein mRNAs. These mitochondrial effects may be part of the progesterone recovery of neurosteroidogenesis. The enzymes 3β-HSD, 3α-HSOR and 5α-reductase are also responsible for the formation of androgens. Because MS patients and EAE rodents show changes of central androgen levels, it is likely that, together with progestins and oestrogens, neuroandrogens afford neuroprotection for EAE and MS. The data reviewed suggest that enhanced synthesis of neurosteroids contributes in an auto/paracrine manner to reinforce the neuroprotective and anti-inflammatory effects of exogenous progesterone given to EAE mice. Fil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Garay, Laura Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Meyer, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Guennoun, Rachida. Université Paris Sud; Francia Fil: Sitruk Ware, R.. The Poputation Council; Estados Unidos Fil: Schumacher, Michael. Inserm; Francia Fil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
- Subjects :
- 0301 basic medicine
endocrine system
medicine.medical_specialty
Encephalomyelitis, Autoimmune, Experimental
Neuroactive steroid
CIENCIAS MÉDICAS Y DE LA SALUD
Endocrinology, Diabetes and Metabolism
Neurociencias
Neuroprotection
NEUROINFLAMMATION
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Translocator protein
Animals
Aromatase
Progesterone
Neuroinflammation
Inflammation
Neurotransmitter Agents
NEUROPROTECTION
biology
Endocrine and Autonomic Systems
Chemistry
Cholesterol side-chain cleavage enzyme
Steroidogenic acute regulatory protein
Experimental autoimmune encephalomyelitis
purl.org/becyt/ford/3.1 [https]
NEUROSTEROIDOGENESIS
PROGESTERONE
medicine.disease
Mitochondria
Medicina Básica
Neuroprotective Agents
030104 developmental biology
biology.protein
purl.org/becyt/ford/3 [https]
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- CONICET Digital (CONICET), Consejo Nacional de Investigaciones Científicas y Técnicas, instacron:CONICET
- Accession number :
- edsair.doi.dedup.....789c31dfa7f02a296e70e8651b090e50