A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure

Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study w...

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Autores: Bedrossiantz, Juliette, Bellot, Marina, Domínguez-García, Pol, Faria, Melissa, Prats, Eva, Gómez-Canela, Cristian, López-Arnau, Raúl, Escubedo, Elena, Raldúa, Demetrio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/257572
Acceso en línea:http://hdl.handle.net/10261/257572
https://api.elsevier.com/content/abstract/scopus_id/85120724631
Access Level:acceso abierto
Palabra clave:Behavior
Gene expression
Methamphetamine neurotoxicity
Neurochemicals
Zebrafish model
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spelling A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine ExposureBedrossiantz, JulietteBellot, MarinaDomínguez-García, PolFaria, MelissaPrats, EvaGómez-Canela, CristianLópez-Arnau, RaúlEscubedo, ElenaRaldúa, DemetrioBehaviorGene expressionMethamphetamine neurotoxicityNeurochemicalsZebrafish modelHyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure. After an initial testing at 20 and 40 mg/L for 48 h, the later METH concentration was selected for developing the model and the effects on the brain monoaminergic profile, locomotor, anxiety-like and social behaviors as well as on the expression of key genes of the catecholaminergic system were determined. A concentration- and time-dependent decrease in the brain levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) was found in METH-exposed fish. A significant hyperactivity was found during the first hour of exposure, followed 3 h after by a positive geotaxis and negative scototaxis in the novel tank and in the light/dark paradigm, respectively. Moreover, the behavioral phenotype in the treated fish was consistent with social isolation. At transcriptional level, th1 and slc18a2 (vmat2) exhibited a significant increase after 3 h of exposure, whereas the expression of gfap, a marker of astroglial response to neuronal injury, was strongly increased after 48 h exposure. However, no evidences of oxidative stress were found in the brain of the treated fish. Altogether, this study demonstrates the suitability of the adult zebrafish as a model of METH-induced neurotoxicity and provides more information about the biochemical and behavioral consequences of METH abuse.This work was supported by Grants PID2020-113371RB-C21 and PID2019-109390RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by ERDF A way of making Europe, as well as by Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033. Moreover, J.B. was supported by Grant PRE2018-083513 funded by MCIN/AEI/10.13039/501100011033 and by ESF Investing in your future. The work was also partially supported by the Catalan Government through the network of recognized research groups (2017 SGR_902 (DR, EP) and 2017SGR979 (RL-A, EE)).Peer reviewedFrontiers MediaMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202220222021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/257572https://api.elsevier.com/content/abstract/scopus_id/85120724631reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MCIN/CEX2018-000794-S/Frontiers in pharmacologyhttps://doi.org/10.3389/fphar.2021.770319Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2575722026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
title A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
spellingShingle A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
Bedrossiantz, Juliette
Behavior
Gene expression
Methamphetamine neurotoxicity
Neurochemicals
Zebrafish model
title_short A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
title_full A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
title_fullStr A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
title_full_unstemmed A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
title_sort A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
dc.creator.none.fl_str_mv Bedrossiantz, Juliette
Bellot, Marina
Domínguez-García, Pol
Faria, Melissa
Prats, Eva
Gómez-Canela, Cristian
López-Arnau, Raúl
Escubedo, Elena
Raldúa, Demetrio
author Bedrossiantz, Juliette
author_facet Bedrossiantz, Juliette
Bellot, Marina
Domínguez-García, Pol
Faria, Melissa
Prats, Eva
Gómez-Canela, Cristian
López-Arnau, Raúl
Escubedo, Elena
Raldúa, Demetrio
author_role author
author2 Bellot, Marina
Domínguez-García, Pol
Faria, Melissa
Prats, Eva
Gómez-Canela, Cristian
López-Arnau, Raúl
Escubedo, Elena
Raldúa, Demetrio
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Behavior
Gene expression
Methamphetamine neurotoxicity
Neurochemicals
Zebrafish model
topic Behavior
Gene expression
Methamphetamine neurotoxicity
Neurochemicals
Zebrafish model
description Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure. After an initial testing at 20 and 40 mg/L for 48 h, the later METH concentration was selected for developing the model and the effects on the brain monoaminergic profile, locomotor, anxiety-like and social behaviors as well as on the expression of key genes of the catecholaminergic system were determined. A concentration- and time-dependent decrease in the brain levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) was found in METH-exposed fish. A significant hyperactivity was found during the first hour of exposure, followed 3 h after by a positive geotaxis and negative scototaxis in the novel tank and in the light/dark paradigm, respectively. Moreover, the behavioral phenotype in the treated fish was consistent with social isolation. At transcriptional level, th1 and slc18a2 (vmat2) exhibited a significant increase after 3 h of exposure, whereas the expression of gfap, a marker of astroglial response to neuronal injury, was strongly increased after 48 h exposure. However, no evidences of oxidative stress were found in the brain of the treated fish. Altogether, this study demonstrates the suitability of the adult zebrafish as a model of METH-induced neurotoxicity and provides more information about the biochemical and behavioral consequences of METH abuse.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/257572
https://api.elsevier.com/content/abstract/scopus_id/85120724631
url http://hdl.handle.net/10261/257572
https://api.elsevier.com/content/abstract/scopus_id/85120724631
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MCIN/CEX2018-000794-S/
Frontiers in pharmacology
https://doi.org/10.3389/fphar.2021.770319
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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