Progesterone treatment modulates mRNA of neurosteroidogenic enzymes in a murine model of multiple sclerosis
| Autor: | Maria Claudia Gonzalez Deniselle, Laura Garay, Paula Anahí González Giqueaux, Alejandro F. De Nicola, Michael Schumacher, Rachida Guennoun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cholestenone 5 alpha-Reductase 17-Hydroxysteroid Dehydrogenases Endocrinology Diabetes and Metabolism Clinical Biochemistry MFN2 Mitochondrion Biochemistry Mice 0302 clinical medicine Endocrinology Progesterone Neurotransmitter Agents NEUROPROTECTION Steroidogenic acute regulatory protein Experimental autoimmune encephalomyelitis NEUROSTEROIDOGENESIS Mitochondria Medicina Básica Spinal Cord EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS Molecular Medicine Female FIS1 endocrine system medicine.medical_specialty Neuroactive steroid 3-Hydroxysteroid Dehydrogenases Encephalomyelitis Autoimmune Experimental Multiple Sclerosis CIENCIAS MÉDICAS Y DE LA SALUD Neurociencias Biology 03 medical and health sciences Internal medicine medicine Translocator protein Animals Cholesterol Side-Chain Cleavage Enzyme RNA Messenger Molecular Biology Cholesterol side-chain cleavage enzyme Cell Biology PROGESTERONE medicine.disease Phosphoproteins Mice Inbred C57BL Microscopy Electron 030104 developmental biology biology.protein 030217 neurology & neurosurgery |
| Popis: | Previous studies of experimental autoimmune encephalomyelitis (EAE) have shown that progesterone decreases inflammatory cell infiltration and proinflammatory factors, increases myelination and attenuates clinical grade of EAE mice. To elucidate potential mediators of these effects, we analyzed the mRNA expression of neurosteroidogenic enzymes in the spinal cord, in view of the protective role of steroids in EAE. We also analyzed mitochondrial morphology and dynamics (fusion and fission proteins), considering the role of mitochondria in neurosteroidogenesis. EAE was induced in C57Bl6 mice using MOG40-54 and killed on day 16 after induction. Using qPCR, we found in steroid-untreated EAE mice decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), P450scc (cholesterol side-chain cleavage), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSD) and aromatase, whereas levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) showed a large intra-group variance. We also found increased mRNA expression of 18Kd translocator protein (TSPO), which likely resulted from the reactive microgliosis in this model. EAE mice also showed pathological mitochondrial morphology and reduced expression of fission and fusion protein mRNAs. Most importantly, pretreatment with progesterone a week before EAE induction increased Star,VDAC, P450scc, 5α-reductase type I, 3α-HSD and aromatase mRNAs and did not modify 3β-HSD. TSPO mRNA was decreased, consequent with the inhibition of microgliosis. Mitochondrial morphology was improved and fission/fusion protein mRNAs were enhanced by progesterone treatment. Furthermore, progesterone protective effects on mitochondrial and endoplasmic reticulum may allow the recovery of neurosteroidogenesis. In this way, endogenously synthesized neurosteroids may reinforce the beneficial effects of exogenous progesterone previously shown in MS mice. 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; Argentina Fil: González Giqueaux, Paula Anahí. 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. Inserm; Francia Fil: Schumacher, Michael. Inserm; Francia Fil: Gonzalez Deniselle, Maria Claudia. Universidad de Buenos Aires; Argentina. 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; Argentina 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; Argentina |
| Databáze: | OpenAIRE |
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