Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1590/1414-431X20133379 http://hdl.handle.net/11449/109480 |
Resumo: | Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes. |
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Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicityCocaineApoptosisNF-BCREBBDNFNeurotoxicityCocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.Instituto de Ciencias Biomedicas, Universidade de Sao Paulo Departamento de FarmacologiaUniversidade Estadual Paulista Faculdade de Ciencias Farmaceuticas Laboratorio de NeuropsicofarmacologiaUniversidade Estadual Paulista Faculdade de Ciencias Farmaceuticas Laboratorio de NeuropsicofarmacologiaAssociação Brasileira de Divulgação Científica (ABRADIC)Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Planeta, Cleopatra da Silva [UNESP]Lepsch, L.b.Alves, R.Scavone, C.2014-09-30T18:18:23Z2014-09-30T18:18:23Z2013-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article909-915application/pdfhttp://dx.doi.org/10.1590/1414-431X20133379Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013.0100-879Xhttp://hdl.handle.net/11449/10948010.1590/1414-431X20133379S0100-879X2013001100909WOS:000328203500001S0100-879X2013001100909.pdf25147625452809420000-0002-1378-6327SciELOreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrazilian Journal of Medical and Biological Research1.492info:eu-repo/semantics/openAccess2024-06-24T14:51:40Zoai:repositorio.unesp.br:11449/109480Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:59:44.172953Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
title |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
spellingShingle |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity Planeta, Cleopatra da Silva [UNESP] Cocaine Apoptosis NF-B CREB BDNF Neurotoxicity |
title_short |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
title_full |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
title_fullStr |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
title_full_unstemmed |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
title_sort |
Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity |
author |
Planeta, Cleopatra da Silva [UNESP] |
author_facet |
Planeta, Cleopatra da Silva [UNESP] Lepsch, L.b. Alves, R. Scavone, C. |
author_role |
author |
author2 |
Lepsch, L.b. Alves, R. Scavone, C. |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Planeta, Cleopatra da Silva [UNESP] Lepsch, L.b. Alves, R. Scavone, C. |
dc.subject.por.fl_str_mv |
Cocaine Apoptosis NF-B CREB BDNF Neurotoxicity |
topic |
Cocaine Apoptosis NF-B CREB BDNF Neurotoxicity |
description |
Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-11-01 2014-09-30T18:18:23Z 2014-09-30T18:18:23Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1590/1414-431X20133379 Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013. 0100-879X http://hdl.handle.net/11449/109480 10.1590/1414-431X20133379 S0100-879X2013001100909 WOS:000328203500001 S0100-879X2013001100909.pdf 2514762545280942 0000-0002-1378-6327 |
url |
http://dx.doi.org/10.1590/1414-431X20133379 http://hdl.handle.net/11449/109480 |
identifier_str_mv |
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 46, n. 11, p. 909-915, 2013. 0100-879X 10.1590/1414-431X20133379 S0100-879X2013001100909 WOS:000328203500001 S0100-879X2013001100909.pdf 2514762545280942 0000-0002-1378-6327 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research 1.492 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
909-915 application/pdf |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica (ABRADIC) |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica (ABRADIC) |
dc.source.none.fl_str_mv |
SciELO reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128732699820032 |