Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/10932 |
Resumo: | Chronic drug use has been associated with changes in gene expression in the brain, yielding long-term neural circuit changes resulting in compulsive behavior or craving. Evidence suggests that the drug may induce complex neuroadaptations after exposure and these changes are mediated by a dynamic pattern of gene regulation. It has been reported that changes in neural circuits begin after the first exposure, altering the expression of genes important for the state of dependence. We studied the gene expression of mRNA (messenger ribonucleic acid) FosB (Bcell homolog of murine osteosarcoma viral oncogene), BDNF (brain-derived neutrophic factor) and DRD5 (dopamine D5 receptor) in dependent patients hospitalized for clinical treatment. For molecular analysis, peripheral blood was collected in an anticoagulant tube, and the extraction of RNA from the lymphocytes did not exceed 2 hours after collection. RNA was used for the synthesis of cDNA (complementary deoxyribonucleic acid) which was amplified by PCR (real-time polymerase chain reaction) using the specific primer. There was a reduced FosB mRNA expression since the fold-change calculated was -1,15 in crack-cocaine dependents (CUD) and -2.17 in alcohol dependents (AUD) compared to non-dependent controls. The Hedge’s effect size gs of the Log FosB/Act was of 0.66 (medium effect size according to Cohen’s convention) the CUD and of 0.3 (small effect size) for the AUD. However, there was an increase in the expression of BDNF and DRD5 mRNAs in both CUD and AUD groups compared to controls. The fold-change of the BDNF mRNA expression for the CUD was 2.25 and 2.0 for the AUD, and the Hedge’s gs effect size of the Log BDNF/Act of 0.35 and 0.36 (small to medium effect size), respectively. The foldchange of DRD5 mRNA expression was 2.22 for both CUD and AUD groups, and the Hedge’s gs effect size of the Log DRD5/Act of 0.25 and 0.26 (small effect size), respectively. These data suggest that it is possible to detect changes in gene expression of central occurrence in lymphocytes present in the peripheral blood and these changes may reflect the molecular changes that occur in neural circuits in drug addiction. |
id |
UFES_f3c09097b062d27965cde92671e50216 |
---|---|
oai_identifier_str |
oai:repositorio.ufes.br:10/10932 |
network_acronym_str |
UFES |
network_name_str |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
repository_id_str |
2108 |
spelling |
Nakamura-Palacios, Ester MiyukiAnders, QuéziaCampos, Fabiana VasconcelosCaldas, Helena Maria da Silva da Costa Correa PereiraGouveia, Sonia Alves2019-03-13T02:04:28Z2019-03-122019-03-13T02:04:28Z2019-02-15Chronic drug use has been associated with changes in gene expression in the brain, yielding long-term neural circuit changes resulting in compulsive behavior or craving. Evidence suggests that the drug may induce complex neuroadaptations after exposure and these changes are mediated by a dynamic pattern of gene regulation. It has been reported that changes in neural circuits begin after the first exposure, altering the expression of genes important for the state of dependence. We studied the gene expression of mRNA (messenger ribonucleic acid) FosB (Bcell homolog of murine osteosarcoma viral oncogene), BDNF (brain-derived neutrophic factor) and DRD5 (dopamine D5 receptor) in dependent patients hospitalized for clinical treatment. For molecular analysis, peripheral blood was collected in an anticoagulant tube, and the extraction of RNA from the lymphocytes did not exceed 2 hours after collection. RNA was used for the synthesis of cDNA (complementary deoxyribonucleic acid) which was amplified by PCR (real-time polymerase chain reaction) using the specific primer. There was a reduced FosB mRNA expression since the fold-change calculated was -1,15 in crack-cocaine dependents (CUD) and -2.17 in alcohol dependents (AUD) compared to non-dependent controls. The Hedge’s effect size gs of the Log FosB/Act was of 0.66 (medium effect size according to Cohen’s convention) the CUD and of 0.3 (small effect size) for the AUD. However, there was an increase in the expression of BDNF and DRD5 mRNAs in both CUD and AUD groups compared to controls. The fold-change of the BDNF mRNA expression for the CUD was 2.25 and 2.0 for the AUD, and the Hedge’s gs effect size of the Log BDNF/Act of 0.35 and 0.36 (small to medium effect size), respectively. The foldchange of DRD5 mRNA expression was 2.22 for both CUD and AUD groups, and the Hedge’s gs effect size of the Log DRD5/Act of 0.25 and 0.26 (small effect size), respectively. These data suggest that it is possible to detect changes in gene expression of central occurrence in lymphocytes present in the peripheral blood and these changes may reflect the molecular changes that occur in neural circuits in drug addiction.O uso crônico de drogas tem sido associado com mudanças na expressão gênica no cérebro, produzindo mudanças nos circuitos neurais à longo prazo, resultando em comportamento compulsivo ou craving. Evidências sugerem que a droga pode induzir neuroadaptações complexas após a exposição e essas alterações são mediadas por um padrão dinâmico de regulação gênica. Tem-se relatado que as mudanças nos circuitos neurais começam após a primeira exposição, alterando a expressão de genes importantes para o estado de dependência. Nós estudamos a expressão gênica do mRNA (ácido ribonucleico mensageiro) FosB (homólogo B do oncogene viral de osteossarcoma murino), BDNF (fator neutrófico derivado do cérebro) e DRD5 (receptor de dopamina D5) em pacientes dependentes internados para tratamento clínico. Para a análise molecular, foi coletado sangue periférico em tubo com anticoagulante e a extração de RNA dos linfócitos não passou de 2 horas após a coleta. O RNA foi usado para a síntese de cDNA (ácido desoxirribonucleico complementar) o qual foi amplificado por PCR (reação em cadeia da polimerase) em tempo real usando o primer específico. Houve uma expressão reduzida de mRNA FosB visto o fold-change calculado ter sido de -1,15 em dependentes de crack-cocaína (CUD) e de -2,17 em dependentes de álcool (AUD) quando comparados a controles não dependentes. O tamanho do efeito gs de Hedge do Log FosB/Act foi de 0,66 (efeito médio de acordo com a convenção de Cohen) para o CUD e 0,3 (efeito pequeno) para o AUD. Entretanto, houve um aumento da expressão dos mRNAs BDNF e DRD5 em ambos grupos CUD e AUD comparados aos controles. O fold-change da expressão de mRNA BDNF para o CUD foi de 2,25 e de 2,0 para o AUD, e o tamanho do efeito gs de Hedge do Log de BDNF/Act foi de 0,35 e 0,36 (efeitos pequenos para médios) respectivamente. O fold-change da expressão do mRNA DRD5 foi de 2,22 para ambos os grupos CUD e AUD, e o tamanho do efeito gs de Hedge do Log de DRD5/Act foi de 0,25 e 0,26 (efeitos pequenos), respectivamente. Esses dados sugerem que é possível a detecção de mudanças da expressão gênica de ocorrência central em linfócitos presentes no sangue periférico e estas mudanças podem refletir as alterações moleculares que ocorrem nos circuitos neurais na dependência química.TextANDERS, Quézia. Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína. 2019.Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Vitória, 2019.http://repositorio.ufes.br/handle/10/10932porUniversidade Federal do Espírito SantoDoutorado em Ciências FisiológicasPrograma de Pós-Graduação em Ciências FisiológicasUFESBRCentro de Ciências da SaúdemRNA expressionFosBBDNFDRD5Expressão mRNAFisiologia612Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaínainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALTese - Quézia Anders Silva.pdfapplication/pdf4047356http://repositorio.ufes.br/bitstreams/35cc7529-c14b-4a83-87a4-4531bf54f403/download90dadc3d576156129b81adf9d9b4c1b1MD5110/109322024-06-27 11:06:11.905oai:repositorio.ufes.br:10/10932http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-06-27T11:06:11Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false |
dc.title.none.fl_str_mv |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
title |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
spellingShingle |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína Anders, Quézia mRNA expression FosB BDNF DRD5 Expressão mRNA Fisiologia 612 |
title_short |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
title_full |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
title_fullStr |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
title_full_unstemmed |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
title_sort |
Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína |
author |
Anders, Quézia |
author_facet |
Anders, Quézia |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nakamura-Palacios, Ester Miyuki |
dc.contributor.author.fl_str_mv |
Anders, Quézia |
dc.contributor.referee1.fl_str_mv |
Campos, Fabiana Vasconcelos |
dc.contributor.referee2.fl_str_mv |
Caldas, Helena Maria da Silva da Costa Correa Pereira |
dc.contributor.referee3.fl_str_mv |
Gouveia, Sonia Alves |
contributor_str_mv |
Nakamura-Palacios, Ester Miyuki Campos, Fabiana Vasconcelos Caldas, Helena Maria da Silva da Costa Correa Pereira Gouveia, Sonia Alves |
dc.subject.eng.fl_str_mv |
mRNA expression |
topic |
mRNA expression FosB BDNF DRD5 Expressão mRNA Fisiologia 612 |
dc.subject.por.fl_str_mv |
FosB BDNF DRD5 Expressão mRNA |
dc.subject.cnpq.fl_str_mv |
Fisiologia |
dc.subject.udc.none.fl_str_mv |
612 |
description |
Chronic drug use has been associated with changes in gene expression in the brain, yielding long-term neural circuit changes resulting in compulsive behavior or craving. Evidence suggests that the drug may induce complex neuroadaptations after exposure and these changes are mediated by a dynamic pattern of gene regulation. It has been reported that changes in neural circuits begin after the first exposure, altering the expression of genes important for the state of dependence. We studied the gene expression of mRNA (messenger ribonucleic acid) FosB (Bcell homolog of murine osteosarcoma viral oncogene), BDNF (brain-derived neutrophic factor) and DRD5 (dopamine D5 receptor) in dependent patients hospitalized for clinical treatment. For molecular analysis, peripheral blood was collected in an anticoagulant tube, and the extraction of RNA from the lymphocytes did not exceed 2 hours after collection. RNA was used for the synthesis of cDNA (complementary deoxyribonucleic acid) which was amplified by PCR (real-time polymerase chain reaction) using the specific primer. There was a reduced FosB mRNA expression since the fold-change calculated was -1,15 in crack-cocaine dependents (CUD) and -2.17 in alcohol dependents (AUD) compared to non-dependent controls. The Hedge’s effect size gs of the Log FosB/Act was of 0.66 (medium effect size according to Cohen’s convention) the CUD and of 0.3 (small effect size) for the AUD. However, there was an increase in the expression of BDNF and DRD5 mRNAs in both CUD and AUD groups compared to controls. The fold-change of the BDNF mRNA expression for the CUD was 2.25 and 2.0 for the AUD, and the Hedge’s gs effect size of the Log BDNF/Act of 0.35 and 0.36 (small to medium effect size), respectively. The foldchange of DRD5 mRNA expression was 2.22 for both CUD and AUD groups, and the Hedge’s gs effect size of the Log DRD5/Act of 0.25 and 0.26 (small effect size), respectively. These data suggest that it is possible to detect changes in gene expression of central occurrence in lymphocytes present in the peripheral blood and these changes may reflect the molecular changes that occur in neural circuits in drug addiction. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-03-13T02:04:28Z |
dc.date.available.fl_str_mv |
2019-03-12 2019-03-13T02:04:28Z |
dc.date.issued.fl_str_mv |
2019-02-15 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ANDERS, Quézia. Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína. 2019.Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Vitória, 2019. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufes.br/handle/10/10932 |
identifier_str_mv |
ANDERS, Quézia. Expressão gênica do mRNA FOSB, BDNF E DRD5 em sangue periférico de dependentes de álcool e crack-cocaína. 2019.Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Vitória, 2019. |
url |
http://repositorio.ufes.br/handle/10/10932 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Doutorado em Ciências Fisiológicas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Fisiológicas |
dc.publisher.initials.fl_str_mv |
UFES |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Doutorado em Ciências Fisiológicas |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) instname:Universidade Federal do Espírito Santo (UFES) instacron:UFES |
instname_str |
Universidade Federal do Espírito Santo (UFES) |
instacron_str |
UFES |
institution |
UFES |
reponame_str |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
collection |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
bitstream.url.fl_str_mv |
http://repositorio.ufes.br/bitstreams/35cc7529-c14b-4a83-87a4-4531bf54f403/download |
bitstream.checksum.fl_str_mv |
90dadc3d576156129b81adf9d9b4c1b1 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 |
repository.name.fl_str_mv |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES) |
repository.mail.fl_str_mv |
|
_version_ |
1804309142487171072 |