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...

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Autores: de Nicola, Alejandro Federico, Garay, Laura Ines, Meyer, Maria, Guennoun, Rachida, Sitruk Ware, R., Schumacher, Michael, Gonzalez Deniselle, Maria Claudia
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
id AR_2a42d141ffbc3205cf7dcffe36634b58
oai_identifier_str oai:ri.conicet.gov.ar:11336/85375
network_acronym_str AR
network_name_str Argentina
repository_id_str
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
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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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