Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice

This article also appears in: Special Collection: COVID-19 Resources.

Detalles Bibliográficos
Autores: Pérez-Taboada, Iara, Alberquilla, Samuel, Martín, Eduardo D., Anand, Rishi, Vietti-Michelina, Stefania, Tebeka, Nchimunya N., Cantley, James, Cragg, Stephanie J., Moratalla, Rosario, Vallejo, Mario
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/222159
Acceso en línea:http://hdl.handle.net/10261/222159
Access Level:acceso abierto
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dc.title.none.fl_str_mv Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
title Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
spellingShingle Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
Pérez-Taboada, Iara
title_short Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
title_full Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
title_fullStr Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
title_full_unstemmed Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
title_sort Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in mice
dc.creator.none.fl_str_mv Pérez-Taboada, Iara
Alberquilla, Samuel
Martín, Eduardo D.
Anand, Rishi
Vietti-Michelina, Stefania
Tebeka, Nchimunya N.
Cantley, James
Cragg, Stephanie J.
Moratalla, Rosario
Vallejo, Mario
author Pérez-Taboada, Iara
author_facet Pérez-Taboada, Iara
Alberquilla, Samuel
Martín, Eduardo D.
Anand, Rishi
Vietti-Michelina, Stefania
Tebeka, Nchimunya N.
Cantley, James
Cragg, Stephanie J.
Moratalla, Rosario
Vallejo, Mario
author_role author
author2 Alberquilla, Samuel
Martín, Eduardo D.
Anand, Rishi
Vietti-Michelina, Stefania
Tebeka, Nchimunya N.
Cantley, James
Cragg, Stephanie J.
Moratalla, Rosario
Vallejo, Mario
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Fundación Ramón Areces
Medical Research Council (UK)
Biotechnology and Biological Sciences Research Council (UK)
Instituto de Salud Carlos III
European Commission
Ministerio de Educación, Cultura y Deporte (España)
Parkinson's Disease Society (UK)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description This article also appears in: Special Collection: COVID-19 Resources.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/222159
url http://hdl.handle.net/10261/222159
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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https://doi.org/10.1002/mds.28124
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dc.publisher.none.fl_str_mv Wiley-VCH
publisher.none.fl_str_mv Wiley-VCH
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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spelling Diabetes causes dysfunctional dopamine neurotransmission favoring nigrostriatal degeneration in micePérez-Taboada, IaraAlberquilla, SamuelMartín, Eduardo D.Anand, RishiVietti-Michelina, StefaniaTebeka, Nchimunya N.Cantley, JamesCragg, Stephanie J.Moratalla, RosarioVallejo, MarioThis article also appears in: Special Collection: COVID-19 Resources.[Background]: Numerous studies indicate an association between neurodegenerative and metabolic diseases. Although still a matter of debate, growing evidence from epidemiological and animal studies indicate that preexisting diabetes increases the risk to develop Parkinson's disease. However, the mechanisms of such an association are unknown.[Objectives]: We investigated whether diabetes alters striatal dopamine neurotransmission and assessed the vulnerability of nigrostriatal neurons to neurodegeneration.[Methods]: We used streptozotocin‐treated and genetically diabetic db/db mice. Expression of oxidative stress and nigrostriatal neuronal markers and levels of dopamine and its metabolites were monitored. Dopamine release and uptake were assessed using fast‐scan cyclic voltammetry. 6‐Hydroxydopamine was unilaterally injected into the striatum using stereotaxic surgery. Motor performance was scored using specific tests.[Results]: Diabetes resulted in oxidative stress and decreased levels of dopamine and its metabolites in the striatum. Levels of proteins regulating dopamine release and uptake, including the dopamine transporter, the Girk2 potassium channel, the vesicular monoamine transporter 2, and the presynaptic vesicle protein synaptobrevin‐2, were decreased in diabetic mice. Electrically evoked levels of extracellular dopamine in the striatum were enhanced, and altered dopamine uptake was observed. Striatal microinjections of a subthreshold dose of the neurotoxin 6‐hydroxydopamine in diabetic mice, insufficient to cause motor alterations in nondiabetic animals, resulted in motor impairment, higher loss of striatal dopaminergic axons, and decreased neuronal cell bodies in the substantia nigra.[Conclusions]: Our results indicate that diabetes promotes striatal oxidative stress, alters dopamine neurotransmission, and increases vulnerability to neurodegenerative damage leading to motor impairment.Funded by the Spanish Ministries of Economy and Competitiveness (grants BFU2014‐52149‐R and BFU2017‐89336‐R to M.V., SAF2016‐78207‐R and PCIN‐2015‐098 to R.M., and BFU2017‐88393‐P to E.D.M.) and of Health, Social Services and Equality (PNSD‐2016I033 to R.M.) and by the Ramón Areces Foundation (ref. 172275 to R.M.). Supported by Medical Research Council UK iCASE award (to S.J.C., R.A.), a Biotechnology and Biological Sciences Research Council UK studentship (to S.V.M.), and Parkinson's UK (J‐1403 to S.J.C.). Partially supported by FEDER funds. CIBERDEM and CIBERNED are initiatives of the Instituto de Salud Carlos III. I.P.T. was supported by a fellowship from the Spanish Ministry of Education, Culture and Sports (FPU 14/04457).Peer reviewedWiley-VCHMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Fundación Ramón ArecesMedical Research Council (UK)Biotechnology and Biological Sciences Research Council (UK)Instituto de Salud Carlos IIIEuropean CommissionMinisterio de Educación, Cultura y Deporte (España)Parkinson's Disease Society (UK)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/222159reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2014‐52149‐Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017‐89336‐RBFU2017‐89336‐R/AEI/10.13039/501100011033info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016‐78207‐Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/PCIN‐2015‐098info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017‐88393‐PBFU2017‐88393‐P/AEI/10.13039/501100011033https://doi.org/10.1002/mds.28124Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2221592026-05-22T06:33:51Z
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