Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits

The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the do...

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Autores: Ortega de San Luís, Clara, Sánchez García, Manuel A., Nieto González, José Luis, García-Junco Clemente, Pablo, Montero Sánchez, Adoración, Fernández-Chacón, Rafael, Pascual, Alberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/79217
Acceso en línea:https://hdl.handle.net/11441/79217
https://doi.org/10.1111/acel.12821
Access Level:acceso abierto
Palabra clave:GDNF
Neurotrophic support
Parkinson’s disease
Shh
Striatal interneurons
Substantia nigra
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spelling Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuitsOrtega de San Luís, ClaraSánchez García, Manuel A.Nieto González, José LuisGarcía-Junco Clemente, PabloMontero Sánchez, AdoraciónFernández-Chacón, RafaelPascual, AlbertoGDNFNeurotrophic supportParkinson’s diseaseShhStriatal interneuronsSubstantia nigraThe striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.Secretaría de Estado de Investigación,Desarrollo e Innovación SAF2012-33816 SAF2015-64111-RAgencia de Innovación y Desarrollo de Andalucía PIE13/00004 CTS2138Ministry of Education AP2010-1598 FPU13 00530Anatomical Society of Great Britain and IrelandFisiología Médica y BiofísicaMinisterio de Economía y Competitividad (MINECO). EspañaJunta de Andalucía2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdftext/htmlhttps://hdl.handle.net/11441/79217https://doi.org/10.1111/acel.12821reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésAging Cell, 17 (5), e12821-1-e12821-14.SAF2012-33816SAF2015-64111-RPIE13/00004CTS2138AP2010-1598FPU1300530http://dx.doi.org/10.1111/acel.12821info:eu-repo/semantics/openAccessoai:idus.us.es:11441/792172026-06-17T12:51:07Z
dc.title.none.fl_str_mv Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
title Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
spellingShingle Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
Ortega de San Luís, Clara
GDNF
Neurotrophic support
Parkinson’s disease
Shh
Striatal interneurons
Substantia nigra
title_short Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
title_full Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
title_fullStr Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
title_full_unstemmed Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
title_sort Substantia nigra dopaminergic neurons and striatalinterneurons are engaged in three parallel but interdependentpostnatal neurotrophic circuits
dc.creator.none.fl_str_mv Ortega de San Luís, Clara
Sánchez García, Manuel A.
Nieto González, José Luis
García-Junco Clemente, Pablo
Montero Sánchez, Adoración
Fernández-Chacón, Rafael
Pascual, Alberto
author Ortega de San Luís, Clara
author_facet Ortega de San Luís, Clara
Sánchez García, Manuel A.
Nieto González, José Luis
García-Junco Clemente, Pablo
Montero Sánchez, Adoración
Fernández-Chacón, Rafael
Pascual, Alberto
author_role author
author2 Sánchez García, Manuel A.
Nieto González, José Luis
García-Junco Clemente, Pablo
Montero Sánchez, Adoración
Fernández-Chacón, Rafael
Pascual, Alberto
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiología Médica y Biofísica
Ministerio de Economía y Competitividad (MINECO). España
Junta de Andalucía
dc.subject.none.fl_str_mv GDNF
Neurotrophic support
Parkinson’s disease
Shh
Striatal interneurons
Substantia nigra
topic GDNF
Neurotrophic support
Parkinson’s disease
Shh
Striatal interneurons
Substantia nigra
description The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/79217
https://doi.org/10.1111/acel.12821
url https://hdl.handle.net/11441/79217
https://doi.org/10.1111/acel.12821
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Aging Cell, 17 (5), e12821-1-e12821-14.
SAF2012-33816
SAF2015-64111-R
PIE13/00004
CTS2138
AP2010-1598
FPU13
00530
http://dx.doi.org/10.1111/acel.12821
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
text/html
dc.publisher.none.fl_str_mv Anatomical Society of Great Britain and Ireland
publisher.none.fl_str_mv Anatomical Society of Great Britain and Ireland
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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