Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal 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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Authors: Ortega-de San Luis, Clara, Sanchez-Garcia, Manuel A, Nieto-Gonzalez, Jose Luis, García-Junco-Clemente, Pablo, Montero-Sanchez, Adoracion, Fernandez-Chacon, Rafael, Pascual, Alberto
Format: article
Publication Date:2018
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25236
Online Access:https://hdl.handle.net/20.500.12105/25236
Access Level:Open access
Keyword:GDNF
Parkinson´s disease
Shh
Neurotrophic support
Striatal interneurons
Substantia nigra
Acetylcholine
Action Potentials
Animals
Animals, Newborn
Cell Survival
Corpus Striatum
Dopaminergic Neurons
Glial Cell Line-Derived Neurotrophic Factor
Hedgehog Proteins
Interneurons
Mice, Inbred C57BL
Mice, Transgenic
Nerve Degeneration
Nerve Net
Signal Transduction
Substantia Nigra
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/25236
network_acronym_str ES
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repository_id_str
spelling Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.Ortega-de San Luis, ClaraSanchez-Garcia, Manuel ANieto-Gonzalez, Jose LuisGarcía-Junco-Clemente, PabloMontero-Sanchez, AdoracionFernandez-Chacon, RafaelPascual, AlbertoGDNFParkinson´s diseaseShhNeurotrophic supportStriatal interneuronsSubstantia nigraAcetylcholineAction PotentialsAnimalsAnimals, NewbornCell SurvivalCorpus StriatumDopaminergic NeuronsGlial Cell Line-Derived Neurotrophic FactorHedgehog ProteinsInterneuronsMice, Inbred C57BLMice, TransgenicNerve DegenerationNerve NetSignal TransductionSubstantia 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.20242024-10-2320182018-07-3020182018-07-30research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/25236reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/252362026-06-12T12:43:37Z
dc.title.none.fl_str_mv Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
title Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
spellingShingle Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
Ortega-de San Luis, Clara
GDNF
Parkinson´s disease
Shh
Neurotrophic support
Striatal interneurons
Substantia nigra
Acetylcholine
Action Potentials
Animals
Animals, Newborn
Cell Survival
Corpus Striatum
Dopaminergic Neurons
Glial Cell Line-Derived Neurotrophic Factor
Hedgehog Proteins
Interneurons
Mice, Inbred C57BL
Mice, Transgenic
Nerve Degeneration
Nerve Net
Signal Transduction
Substantia Nigra
title_short Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
title_full Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
title_fullStr Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
title_full_unstemmed Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
title_sort Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.
dc.creator.none.fl_str_mv Ortega-de San Luis, Clara
Sanchez-Garcia, Manuel A
Nieto-Gonzalez, Jose Luis
García-Junco-Clemente, Pablo
Montero-Sanchez, Adoracion
Fernandez-Chacon, Rafael
Pascual, Alberto
author Ortega-de San Luis, Clara
author_facet Ortega-de San Luis, Clara
Sanchez-Garcia, Manuel A
Nieto-Gonzalez, Jose Luis
García-Junco-Clemente, Pablo
Montero-Sanchez, Adoracion
Fernandez-Chacon, Rafael
Pascual, Alberto
author_role author
author2 Sanchez-Garcia, Manuel A
Nieto-Gonzalez, Jose Luis
García-Junco-Clemente, Pablo
Montero-Sanchez, Adoracion
Fernandez-Chacon, Rafael
Pascual, Alberto
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv GDNF
Parkinson´s disease
Shh
Neurotrophic support
Striatal interneurons
Substantia nigra
Acetylcholine
Action Potentials
Animals
Animals, Newborn
Cell Survival
Corpus Striatum
Dopaminergic Neurons
Glial Cell Line-Derived Neurotrophic Factor
Hedgehog Proteins
Interneurons
Mice, Inbred C57BL
Mice, Transgenic
Nerve Degeneration
Nerve Net
Signal Transduction
Substantia Nigra
topic GDNF
Parkinson´s disease
Shh
Neurotrophic support
Striatal interneurons
Substantia nigra
Acetylcholine
Action Potentials
Animals
Animals, Newborn
Cell Survival
Corpus Striatum
Dopaminergic Neurons
Glial Cell Line-Derived Neurotrophic Factor
Hedgehog Proteins
Interneurons
Mice, Inbred C57BL
Mice, Transgenic
Nerve Degeneration
Nerve Net
Signal Transduction
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
2018-07-30
2018
2018-07-30
2024
2024-10-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/25236
url https://hdl.handle.net/20.500.12105/25236
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421100164710400
score 15,812429

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