Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos

Detalhes bibliográficos
Autor(a) principal: Santos, Gabriel Victoriano dos
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/10664
Resumo: Recent findings have demonstrated that the medial prefrontal cortex (mPFC) has a lateralized role in the control of response to stressors, and the left hemisphere (LmPFC) would attenuate the anxiogenic responses elicited by right medial prefrontal cortex (RmPFC). The temporary chemical inactivation of LmPFC, followed by social defeat stress (SDS)provokes an anxiogenic effect that persists for up to 24 hours in mice. In the present study, we investigated: (1) the anxiety levels of mice exposed to the elevated plus maze (EPM) 2, 5 or 10 days after the combination SDS + LmPFC inactivation and (2) the role of the glutamate NMDA (n-methyl-D-aspartate) receptors located in the RmPFC in anxiety-related behaviors in mice exposed to the EPM two days after the combination “SDS + LmPFC inactivation”. Male Swiss mice received intra-LmPFC microinjection of saline or cobalt chloride (CoCl2, non-specific synaptic inhibitor) and were exposed to acute SDS or non-aggressive interaction. Two, five or 10 days later, they were exposed to the EPM to assess conventional anxiety [percentage of open arm entries and percentage of open arm time (%OE; %OT)] and complementary [Stretched attend posture frequencies in protected (pSAP) and unprotected (uSAP) places and protected Head-dipping (pHD) and unprotected (uHD) places] measures. Locomotor activity [frequency of closed-arms entries (CE)] was also recorded. The results showed that the association "inactivation of LmPFC + SDS" decreased %OE and %OT, increased pSAP and decreased uSAP and uHD in almost all testing days. In experiment 2, two days after receiving intra-LmPFC CoCl2 or saline + SDS, the animals received intra- RmPFC microinjection of saline or AP7 (NMDA receptor antagonist) 10 minutes before being exposed to the EPM. Results showed that the CoCl2 + SDS combination confirmed the anxiogenic effect, however only in the animals treated with saline in the LmPFC. CE was remained unchanged in both experiments. These results suggest that the inactivation of the LmPFC may prolong to up to 10 days the anxiogenic-like effects induced by SDS. Interestingly, this type of stress-induced anxiogenesis is impaired by the blockade of the NMDA receptor located in the RmPFC of mice.
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spelling Santos, Gabriel Victoriano dosSouza, Ricardo Luiz Nunes dehttp://lattes.cnpq.br/2475842684688693http://lattes.cnpq.br/2950857821458547a9b1249a-2abd-4118-ad36-76f1a6565e5a2018-11-12T22:27:15Z2018-11-12T22:27:15Z2018-10-18SANTOS, Gabriel Victoriano dos. Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos. 2018. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10664.https://repositorio.ufscar.br/handle/ufscar/10664Recent findings have demonstrated that the medial prefrontal cortex (mPFC) has a lateralized role in the control of response to stressors, and the left hemisphere (LmPFC) would attenuate the anxiogenic responses elicited by right medial prefrontal cortex (RmPFC). The temporary chemical inactivation of LmPFC, followed by social defeat stress (SDS)provokes an anxiogenic effect that persists for up to 24 hours in mice. In the present study, we investigated: (1) the anxiety levels of mice exposed to the elevated plus maze (EPM) 2, 5 or 10 days after the combination SDS + LmPFC inactivation and (2) the role of the glutamate NMDA (n-methyl-D-aspartate) receptors located in the RmPFC in anxiety-related behaviors in mice exposed to the EPM two days after the combination “SDS + LmPFC inactivation”. Male Swiss mice received intra-LmPFC microinjection of saline or cobalt chloride (CoCl2, non-specific synaptic inhibitor) and were exposed to acute SDS or non-aggressive interaction. Two, five or 10 days later, they were exposed to the EPM to assess conventional anxiety [percentage of open arm entries and percentage of open arm time (%OE; %OT)] and complementary [Stretched attend posture frequencies in protected (pSAP) and unprotected (uSAP) places and protected Head-dipping (pHD) and unprotected (uHD) places] measures. Locomotor activity [frequency of closed-arms entries (CE)] was also recorded. The results showed that the association "inactivation of LmPFC + SDS" decreased %OE and %OT, increased pSAP and decreased uSAP and uHD in almost all testing days. In experiment 2, two days after receiving intra-LmPFC CoCl2 or saline + SDS, the animals received intra- RmPFC microinjection of saline or AP7 (NMDA receptor antagonist) 10 minutes before being exposed to the EPM. Results showed that the CoCl2 + SDS combination confirmed the anxiogenic effect, however only in the animals treated with saline in the LmPFC. CE was remained unchanged in both experiments. These results suggest that the inactivation of the LmPFC may prolong to up to 10 days the anxiogenic-like effects induced by SDS. Interestingly, this type of stress-induced anxiogenesis is impaired by the blockade of the NMDA receptor located in the RmPFC of mice.Recentes evidências sugestivas apontam que o Córtex Pré-Frontal medial (CPFm) possui um papel lateralizado na resposta a eventos estressores, sendo que o hemisfério esquerdo (CPFmE) atenuaria as respostas ansiogênicas comandadas pelo direito (CPFmD). A inativação química temporária do CPFmE, seguida pelo estresse de derrota social (EDS), repercute em respostas ansiogênicas que perduram por 24 horas em camundongos. No presente estudo, investigamos: (1) os níveis de ansiedade de camundongos expostos ao labirinto em cruz elevado (LCE) 2, 5 e 10 dias após o EDS sob inativação do CPFmE e se o (2) os receptores glutamatérgicos do tipo NMDA (n-metil-D-aspartato) localizados no CPFmD desenvolvem algum papel nesse processo. Camundongos Suíços machos receberam microinjeção intra-CPFmE de salina ou cloreto de cobalto (CoCl2, inibidor sináptico inespecífico) e foram submetidos ao EDS agudo ou interação não agressiva. Dois, cinco ou 10 dias depois, foram expostos ao LCE para avaliação das medidas convencionais de ansiedade [porcentagem de entradas e tempo nos braços abertos (%EBA; %TBA)], atividade locomotora [frequência de entradas nos braços fechados (EBF)] e medidas complementares [frequências de Stretched attend posture em ambientes protegidos (SAPp) e desprotegidos (SAPd) e Head-dipping protegidos (HDp) e desprotegidos (HDd)]. Os resultados demonstraram que a associação “inativação do CPFmE + EDS” reduziu %EBA e %TBA, sem alterar EBF, aumentou o SAPp nos 2º e 5º dias, diminuiu SAPd apenas no 5º dia e reduziu o HDd em todos os tempos analisados. No experimento 2, dois dias após receberem a combinação CoCl2 ou salina no CPFmE e o EDS, foi realizada a microinjeção intra-CPFmD de salina ou AP7 (antagonista de receptor NMDA) 10 minutos antes da exposição dos camundongos ao LCE. Assim, a combinação CoCl2 + EDS confirmou a ansiogênese, porém somente nos animais tratados com salina no CPFmD. Esses resultados sugerem que a inativação do CPFmE pode tornar os animais susceptíveis ao EDS, repercutindo em respostas relacionadas a ansiedade por até 10 dias. Entretanto, esse efeito ansiogênico pode ser revertido pelos bloqueios dos receptores NMDA no CPFmDCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: 001porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarAnsiedadeCórtex pré-frontal medialLateralização funcionalEstresse de derrota socialCamundongosAnxietyMedial prefrontal cortexFunctional lateralizationSocial defeat stressMiceCIENCIAS BIOLOGICAS::FISIOLOGIAPapel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongosThe role of the medial prefrontal cortex in the anxiogenesis induced by the social defeat stress in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisOnlineae9fb443-1bf9-43ac-8dab-58db44bbe2efinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDissertação Gabriel Victoriano Final.pdfDissertação Gabriel Victoriano Final.pdfDissertação Finalapplication/pdf1311683https://repositorio.ufscar.br/bitstream/ufscar/10664/1/Disserta%c3%a7%c3%a3o%20Gabriel%20Victoriano%20Final.pdfc4021593b112533ce3413465946fee11MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/10664/4/license.txtae0398b6f8b235e40ad82cba6c50031dMD54TEXTDissertação Gabriel Victoriano Final.pdf.txtDissertação Gabriel Victoriano Final.pdf.txtExtracted texttext/plain150856https://repositorio.ufscar.br/bitstream/ufscar/10664/5/Disserta%c3%a7%c3%a3o%20Gabriel%20Victoriano%20Final.pdf.txt4f7825844edcab9d3b051b699f3a187cMD55THUMBNAILDissertação Gabriel Victoriano Final.pdf.jpgDissertação Gabriel Victoriano Final.pdf.jpgIM Thumbnailimage/jpeg6183https://repositorio.ufscar.br/bitstream/ufscar/10664/6/Disserta%c3%a7%c3%a3o%20Gabriel%20Victoriano%20Final.pdf.jpg6a78e9594003b6505bd1391c44f9410aMD56ufscar/106642023-09-18 18:31:17.713oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:17Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
dc.title.alternative.eng.fl_str_mv The role of the medial prefrontal cortex in the anxiogenesis induced by the social defeat stress in mice
title Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
spellingShingle Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
Santos, Gabriel Victoriano dos
Ansiedade
Córtex pré-frontal medial
Lateralização funcional
Estresse de derrota social
Camundongos
Anxiety
Medial prefrontal cortex
Functional lateralization
Social defeat stress
Mice
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
title_full Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
title_fullStr Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
title_full_unstemmed Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
title_sort Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
author Santos, Gabriel Victoriano dos
author_facet Santos, Gabriel Victoriano dos
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/2950857821458547
dc.contributor.author.fl_str_mv Santos, Gabriel Victoriano dos
dc.contributor.advisor1.fl_str_mv Souza, Ricardo Luiz Nunes de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2475842684688693
dc.contributor.authorID.fl_str_mv a9b1249a-2abd-4118-ad36-76f1a6565e5a
contributor_str_mv Souza, Ricardo Luiz Nunes de
dc.subject.por.fl_str_mv Ansiedade
Córtex pré-frontal medial
Lateralização funcional
Estresse de derrota social
Camundongos
topic Ansiedade
Córtex pré-frontal medial
Lateralização funcional
Estresse de derrota social
Camundongos
Anxiety
Medial prefrontal cortex
Functional lateralization
Social defeat stress
Mice
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Anxiety
Medial prefrontal cortex
Functional lateralization
Social defeat stress
Mice
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description Recent findings have demonstrated that the medial prefrontal cortex (mPFC) has a lateralized role in the control of response to stressors, and the left hemisphere (LmPFC) would attenuate the anxiogenic responses elicited by right medial prefrontal cortex (RmPFC). The temporary chemical inactivation of LmPFC, followed by social defeat stress (SDS)provokes an anxiogenic effect that persists for up to 24 hours in mice. In the present study, we investigated: (1) the anxiety levels of mice exposed to the elevated plus maze (EPM) 2, 5 or 10 days after the combination SDS + LmPFC inactivation and (2) the role of the glutamate NMDA (n-methyl-D-aspartate) receptors located in the RmPFC in anxiety-related behaviors in mice exposed to the EPM two days after the combination “SDS + LmPFC inactivation”. Male Swiss mice received intra-LmPFC microinjection of saline or cobalt chloride (CoCl2, non-specific synaptic inhibitor) and were exposed to acute SDS or non-aggressive interaction. Two, five or 10 days later, they were exposed to the EPM to assess conventional anxiety [percentage of open arm entries and percentage of open arm time (%OE; %OT)] and complementary [Stretched attend posture frequencies in protected (pSAP) and unprotected (uSAP) places and protected Head-dipping (pHD) and unprotected (uHD) places] measures. Locomotor activity [frequency of closed-arms entries (CE)] was also recorded. The results showed that the association "inactivation of LmPFC + SDS" decreased %OE and %OT, increased pSAP and decreased uSAP and uHD in almost all testing days. In experiment 2, two days after receiving intra-LmPFC CoCl2 or saline + SDS, the animals received intra- RmPFC microinjection of saline or AP7 (NMDA receptor antagonist) 10 minutes before being exposed to the EPM. Results showed that the CoCl2 + SDS combination confirmed the anxiogenic effect, however only in the animals treated with saline in the LmPFC. CE was remained unchanged in both experiments. These results suggest that the inactivation of the LmPFC may prolong to up to 10 days the anxiogenic-like effects induced by SDS. Interestingly, this type of stress-induced anxiogenesis is impaired by the blockade of the NMDA receptor located in the RmPFC of mice.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-11-12T22:27:15Z
dc.date.available.fl_str_mv 2018-11-12T22:27:15Z
dc.date.issued.fl_str_mv 2018-10-18
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv SANTOS, Gabriel Victoriano dos. Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos. 2018. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10664.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/10664
identifier_str_mv SANTOS, Gabriel Victoriano dos. Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos. 2018. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10664.
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Câmpus São Carlos
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dc.publisher.initials.fl_str_mv UFSCar
publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
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