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 documento: artigo
Data de publicação:2021
País:España
Recursos:Universitat Ramon Llull (URL)
Repositório:DAU Arxiu Digital de la Universitat Ramon Llull
OAI Identifier:oai:dau.url.edu:20.500.14342/4401
Acesso em linha:https://hdl.handle.net/20.500.14342/4401
https://doi.org/10.3389/fphar.2021.770319
Access Level:Acceso aberto
Palavra-chave:Methamphetamine neurotoxicity
Zebrafish model
Behavior
Neurochemicals
Gene expression
Metamfetamina
Neurotoxines
Hàbits i conducta
Neuroquímica
Expressió gènica
577
612
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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, DemetrioMethamphetamine neurotoxicityZebrafish modelBehaviorNeurochemicalsGene expressionMetamfetaminaNeurotoxinesHàbits i conductaNeuroquímicaExpressió gènica577612Hyperthermia 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.info:eu-repo/semantics/publishedVersionFrontiers MediaUniversitat Ramon Llull. IQS202420242021info:eu-repo/semantics/article16 p.application/pdfhttps://hdl.handle.net/20.500.14342/4401https://doi.org/10.3389/fphar.2021.770319reponame:DAU Arxiu Digital de la Universitat Ramon Llullinstname:Universitat Ramon Llull (URL)InglésFrontiers in Pharmacologyinfo:eu-repo/grantAgreement/AEI-MCI/PN I+D/PID2020-113371RB-C21info:eu-repo/grantAgreement/AEI-MCI/PN I+D/PID2019-109390RB-I00info:eu-repo/grantAgreement/AEI-MCI/PN I+D/CEX2018-000794-Sinfo:eu-repo/grantAgreement/AEI-MCI/PN I+D/PRE2018-083513info:eu-repo/grantAgreement/DEC/SGR/2017 SGR_902info:eu-repo/grantAgreement/DEC/SGR/2017SGR979© L'autor/aAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dau.url.edu:20.500.14342/44012026-06-21T06:40:37Z
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
Methamphetamine neurotoxicity
Zebrafish model
Behavior
Neurochemicals
Gene expression
Metamfetamina
Neurotoxines
Hàbits i conducta
Neuroquímica
Expressió gènica
577
612
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 Universitat Ramon Llull. IQS
dc.subject.none.fl_str_mv Methamphetamine neurotoxicity
Zebrafish model
Behavior
Neurochemicals
Gene expression
Metamfetamina
Neurotoxines
Hàbits i conducta
Neuroquímica
Expressió gènica
577
612
topic Methamphetamine neurotoxicity
Zebrafish model
Behavior
Neurochemicals
Gene expression
Metamfetamina
Neurotoxines
Hàbits i conducta
Neuroquímica
Expressió gènica
577
612
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
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14342/4401
https://doi.org/10.3389/fphar.2021.770319
url https://hdl.handle.net/20.500.14342/4401
https://doi.org/10.3389/fphar.2021.770319
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Frontiers in Pharmacology
info:eu-repo/grantAgreement/AEI-MCI/PN I+D/PID2020-113371RB-C21
info:eu-repo/grantAgreement/AEI-MCI/PN I+D/PID2019-109390RB-I00
info:eu-repo/grantAgreement/AEI-MCI/PN I+D/CEX2018-000794-S
info:eu-repo/grantAgreement/AEI-MCI/PN I+D/PRE2018-083513
info:eu-repo/grantAgreement/DEC/SGR/2017 SGR_902
info:eu-repo/grantAgreement/DEC/SGR/2017SGR979
dc.rights.none.fl_str_mv © L'autor/a
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © L'autor/a
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DAU Arxiu Digital de la Universitat Ramon Llull
instname:Universitat Ramon Llull (URL)
instname_str Universitat Ramon Llull (URL)
reponame_str DAU Arxiu Digital de la Universitat Ramon Llull
collection DAU Arxiu Digital de la Universitat Ramon Llull
repository.name.fl_str_mv
repository.mail.fl_str_mv
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