Papel do córtex pré-frontal medial na ansiogênese induzida pelo estresse de derrota social em camundongos
Autor(a) principal: | |
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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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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. |
url |
https://repositorio.ufscar.br/handle/ufscar/10664 |
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openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Carlos Câmpus São Carlos |
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Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCF |
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UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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