Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects
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 neurosteroid...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/85375 |
| Acceso en línea: | http://hdl.handle.net/11336/85375 |
| Access Level: | acceso abierto |
| Palabra clave: | NEUROINFLAMMATION NEUROPROTECTION NEUROSTEROIDOGENESIS PROGESTERONE https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
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Argentina |
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| dc.title.none.fl_str_mv |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| title |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| spellingShingle |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects de Nicola, Alejandro Federico NEUROINFLAMMATION NEUROPROTECTION NEUROSTEROIDOGENESIS PROGESTERONE https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| title_short |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| title_full |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| title_fullStr |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| title_full_unstemmed |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| title_sort |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects |
| dc.creator.none.fl_str_mv |
de Nicola, Alejandro Federico Garay, Laura Ines Meyer, Maria Guennoun, Rachida Sitruk Ware, R. Schumacher, Michael Gonzalez Deniselle, Maria Claudia |
| author |
de Nicola, Alejandro Federico |
| author_facet |
de Nicola, Alejandro Federico Garay, Laura Ines Meyer, Maria Guennoun, Rachida Sitruk Ware, R. Schumacher, Michael Gonzalez Deniselle, Maria Claudia |
| author_role |
author |
| author2 |
Garay, Laura Ines Meyer, Maria Guennoun, Rachida Sitruk Ware, R. Schumacher, Michael Gonzalez Deniselle, Maria Claudia |
| author2_role |
author author author author author author |
| dc.subject.none.fl_str_mv |
NEUROINFLAMMATION NEUROPROTECTION NEUROSTEROIDOGENESIS PROGESTERONE https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| topic |
NEUROINFLAMMATION NEUROPROTECTION NEUROSTEROIDOGENESIS PROGESTERONE https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| description |
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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-02 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/85375 de Nicola, Alejandro Federico; Garay, Laura Ines; Meyer, Maria; Guennoun, Rachida; Sitruk Ware, R.; et al.; Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects; Wiley Blackwell Publishing, Inc; Journal of Neuroendocrinology; 30; 2; 2-2018 0953-8194 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/85375 |
| identifier_str_mv |
de Nicola, Alejandro Federico; Garay, Laura Ines; Meyer, Maria; Guennoun, Rachida; Sitruk Ware, R.; et al.; Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects; Wiley Blackwell Publishing, Inc; Journal of Neuroendocrinology; 30; 2; 2-2018 0953-8194 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1111/jne.12502 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
| publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1799195578940260352 |
| spelling |
Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effectsde Nicola, Alejandro FedericoGaray, Laura InesMeyer, MariaGuennoun, RachidaSitruk Ware, R.Schumacher, MichaelGonzalez Deniselle, Maria ClaudiaNEUROINFLAMMATIONNEUROPROTECTIONNEUROSTEROIDOGENESISPROGESTERONEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Progesterone 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: Guennoun, Rachida. Université Paris Sud; FranciaFil: Sitruk Ware, R.. The Poputation Council; Estados UnidosFil: Schumacher, Michael. Inserm; FranciaFil: 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; ArgentinaWiley Blackwell Publishing, Inc2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85375de Nicola, Alejandro Federico; Garay, Laura Ines; Meyer, Maria; Guennoun, Rachida; Sitruk Ware, R.; et al.; Neurosteroidogenesis and progesterone anti-inflammatory/neuroprotective effects; Wiley Blackwell Publishing, Inc; Journal of Neuroendocrinology; 30; 2; 2-20180953-8194CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/jne.12502info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:56:54Zoai:ri.conicet.gov.ar:11336/85375instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:56:54.883CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
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15.811543 |