Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/18777 |
Resumo: | The lateral hypothalamus (LH) is a hypothalamic area implicated in the integration of physiological and behavioral responses to stress. Indeed, it has been demonstrated the involvement of the LH in cardiovascular responses to stress and in the control of behavioral responses related to anxiety and depression. The corticotropin-releasing factor (CRF) system has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments induced by exposure to aversive situations. In addition, chronic exposure to aversive situations affects the expression of CRF components in brain regions involved in the control of stress responses. Therefore, the hypothesis of our work was that the CRF neurotransmission present in the LH is involved in the cardiovascular and anxiety-like behavioral changes induced by acute or repeated restraint stress, as well as in the cardiovascular changes induced by chronic variable stress (CVS). Initially, we investigated the effect of bilateral microinjection of the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine-30 (ASV-30) on cardiovascular responses during acute restraint stress. It was identified that microinjection of CP376395 or ASV-30 into the LH decreased the tachycardia response during an acute session of restraint stress, but without altering the pressor responses and tail skin temperature drop. We also compared the effect of LH treatment with CRF1 or CRF2 receptor antagonists on cardiovascular responses during the 1st and 10th session of restraint stress. As observed in the acutely stressed animals, we identified that treatment of the LH with CP376395 or ASV-30 reduced the tachycardia response during the 10th restraint stress session. Furthermore, treatment of the HL with CP376395 increased the tail skin temperature drop response during the 10th restraint session. In addition, we evaluated the involvement of LH CRF1 and CRF2 receptors in the control of anxiety-like behavior induced by an acute or 10 sessions of restraint stress. We identified that treatment of the LH with CP376395 or ASV-30 inhibited the ansiogenic-like effect in the elevated plus maze (EPM) induced by the acute session of restraint stress. We did not identify behavioral changes in the EPM in animals repeatedly subjected to restraint stress, and pharmacological treatments also had no behavioral effect when administered before the 10th restraint session. The evaluation of the influence of the CRF system on the cardiovascular changes induced by CVS indicated that antagonism of either CRF1 or CRF2 receptors in the LH prevented the impairment in baroreflex activity observed in animals subjected to CVS. Finally, the effect of exposure to repeated restraint stress (RRS) or CVS on protein levels of CRF receptors in the LH was assessed. It was observed that RRS had no influence on the levels of both CRF receptors, but CVS caused an increase in CRF2 receptor protein levels, but without altering CRF1 receptor levels. In summary, the data of the present study indicate that CRF neurotransmission in the LH mediates cardiovascular and behavioral responses to acute and chronic stress. |
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Barretto-de-Souza, LucasCrestani, Carlos Cesarhttp://lattes.cnpq.br/1117432571971568http://lattes.cnpq.br/5795792232582121https://orcid.org/0000-0003-1589-3297https://orcid.org/0000-0002-1942-858X6228fffc-0fe8-4842-9918-1bcdf36b1ebe2023-10-17T13:15:30Z2023-10-17T13:15:30Z2023-09-26BARRETTO-DE-SOUZA, Lucas. Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos. 2023. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/ufscar/18777.https://repositorio.ufscar.br/handle/ufscar/18777The lateral hypothalamus (LH) is a hypothalamic area implicated in the integration of physiological and behavioral responses to stress. Indeed, it has been demonstrated the involvement of the LH in cardiovascular responses to stress and in the control of behavioral responses related to anxiety and depression. The corticotropin-releasing factor (CRF) system has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments induced by exposure to aversive situations. In addition, chronic exposure to aversive situations affects the expression of CRF components in brain regions involved in the control of stress responses. Therefore, the hypothesis of our work was that the CRF neurotransmission present in the LH is involved in the cardiovascular and anxiety-like behavioral changes induced by acute or repeated restraint stress, as well as in the cardiovascular changes induced by chronic variable stress (CVS). Initially, we investigated the effect of bilateral microinjection of the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine-30 (ASV-30) on cardiovascular responses during acute restraint stress. It was identified that microinjection of CP376395 or ASV-30 into the LH decreased the tachycardia response during an acute session of restraint stress, but without altering the pressor responses and tail skin temperature drop. We also compared the effect of LH treatment with CRF1 or CRF2 receptor antagonists on cardiovascular responses during the 1st and 10th session of restraint stress. As observed in the acutely stressed animals, we identified that treatment of the LH with CP376395 or ASV-30 reduced the tachycardia response during the 10th restraint stress session. Furthermore, treatment of the HL with CP376395 increased the tail skin temperature drop response during the 10th restraint session. In addition, we evaluated the involvement of LH CRF1 and CRF2 receptors in the control of anxiety-like behavior induced by an acute or 10 sessions of restraint stress. We identified that treatment of the LH with CP376395 or ASV-30 inhibited the ansiogenic-like effect in the elevated plus maze (EPM) induced by the acute session of restraint stress. We did not identify behavioral changes in the EPM in animals repeatedly subjected to restraint stress, and pharmacological treatments also had no behavioral effect when administered before the 10th restraint session. The evaluation of the influence of the CRF system on the cardiovascular changes induced by CVS indicated that antagonism of either CRF1 or CRF2 receptors in the LH prevented the impairment in baroreflex activity observed in animals subjected to CVS. Finally, the effect of exposure to repeated restraint stress (RRS) or CVS on protein levels of CRF receptors in the LH was assessed. It was observed that RRS had no influence on the levels of both CRF receptors, but CVS caused an increase in CRF2 receptor protein levels, but without altering CRF1 receptor levels. In summary, the data of the present study indicate that CRF neurotransmission in the LH mediates cardiovascular and behavioral responses to acute and chronic stress.O hipotálamo lateral (HL) é uma área hipotalâmica implicada na integração das respostas fisiológicas e comportamentais ao estresse. De fato, foi demonstrado o envolvimento do HL nas respostas cardiovasculares ao estresse e no controle de respostas comportamentais relacionadas à ansiedade e depressão. O sistema do fator liberador de corticotrofina (CRF) foi demonstrado ser um importante mecanismo neuroquímico no sistema nervoso central envolvido na etiologia das alterações comportamentais e nos ajustes fisiológicos induzidos pela exposição a situações aversivas. Além disso, a exposição crônica a situações aversivas afeta a expressão dos componentes do sistema “CRFérgico” em regiões encefálicas envolvidas no controle das respostas ao estresse. Assim, a hipótese de nosso trabalho foi que a neurotransmissão “CRFérgica” presente no HL está envolvida nas alterações cardiovasculares e comportamentais relacionadas à ansiedade induzidas pelo estresse de restrição agudo ou repetido, assim como nas alterações cardiovasculares induzidas pelo estresse crônico variável (ECV). Inicialmente, investigamos o efeito da microinjeção bilateral de CP376395 (antagonista seletivo do receptor CRF1) ou antisauvagine-30 (ASV-30; antagonista seletivo do receptor CRF2) nas respostas cardiovasculares durante o estresse de restrição agudo. Foi identificado que a microinjeção de CP376395 ou ASV-30 diminuiu a resposta de taquicardia durante uma sessão aguda de estresse de restrição, porém sem alterar as respostas pressora e a queda de temperatura cutânea da cauda. Nós também comparamos o efeito do tratamento do HL com os antagonistas dos receptores CRF1 ou CRF2 sobre as respostas cardiovasculares durante a 1º e a 10º sessão de estresse de restrição. Assim como observado nos animais estressados agudamente, nós identificamos que o tratamento do HL com CP376395 ou ASV-30 reduziu a resposta de taquicardia durante a 10º sessão de estresse de restrição. Além disso, o tratamento do HL com CP376395 aumentou a resposta de queda da temperatura cutânea da cauda durante a 10º sessão de restrição. Adicionalmente, foi realizada a avaliação do envolvimento dos receptores CRF1 e CRF2 do HL no controle do comportamento do tipo ansioso induzido por uma sessão aguda ou 10 sessões de estresse de restrição. Nós identificamos que o tratamento do HL com CP376395 ou ASV-30 inibiu a resposta comportamental do tipo ansiogênica avaliada no labirinto em cruz elevado (LCE) desencadeada pela sessão aguda de estresse de restrição. Nós não identificamos alterações comportamentais no LCE nos animais submetidos repetidamente ao estresse de restrição, e os tratamentos farmacológicos também não tiveram nenhum efeito comportamental quando administrados antes da 10º sessão de restrição. A avaliação da influência do sistema “CRFérgico” nas alterações cardiovasculares induzidas pelo ECV indicou que o antagonismo dos receptores CRF1 ou CRF2 no HL evitou o prejuízo na atividade barorreflexa observada nos animais submetidos ao ECV. Por fim, foi avaliado o efeito da exposição ao estresse repetido de restrição (ERR) ou ao ECV sobre os níveis proteicos dos receptores “CRFérgicos” no HL. Foi observado que o ERR não teve influência nos níveis de ambos os receptores CRFérgicos, porém o ECV promoveu um aumento dos níveis proteicos do receptor CRF2, sem alterar os níveis do receptor CRF1. Em suma, os dados do presente estudo indicam que a neurotransmissão “CRFérgica” no HL participa do controle de respostas cardiovasculares e comportamentais ao estresse agudo e crônico.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Processo nº 2018/14284-4, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Processo nº 164856/2018-8, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessHipotálamoCRFEstresseCardiovascularAnsiedadeHypothalamusCRFCardiovascularAnxietyCIENCIAS BIOLOGICAS::FARMACOLOGIACIENCIAS BIOLOGICAS::FISIOLOGIACIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA CARDIOVASCULAREnvolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratosInvolvement of corticotropin-releasing factor (CRF) neurotransmission in the lateral hypothalamus in cardiovascular and behavioral responses to stress in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis60060065604e0e-ddb0-417b-af11-12d9af9d2db3reponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTese Lucas Barretto de Souza.pdfTese Lucas Barretto de Souza.pdfTese - Lucas Barretto de Souzaapplication/pdf9102750https://repositorio.ufscar.br/bitstream/ufscar/18777/1/Tese%20Lucas%20Barretto%20de%20Souza.pdf9136bf97d0d56f943a14c5c41eb97210MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8810https://repositorio.ufscar.br/bitstream/ufscar/18777/3/license_rdff337d95da1fce0a22c77480e5e9a7aecMD53TEXTTese Lucas Barretto de Souza.pdf.txtTese Lucas Barretto de Souza.pdf.txtExtracted texttext/plain214845https://repositorio.ufscar.br/bitstream/ufscar/18777/4/Tese%20Lucas%20Barretto%20de%20Souza.pdf.txt7b91f37ee71ff1824fdaf1e7ff0b6213MD54ufscar/187772024-05-14 17:13:16.817oai:repositorio.ufscar.br:ufscar/18777Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222024-05-14T17:13:16Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
dc.title.alternative.eng.fl_str_mv |
Involvement of corticotropin-releasing factor (CRF) neurotransmission in the lateral hypothalamus in cardiovascular and behavioral responses to stress in rats |
title |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
spellingShingle |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos Barretto-de-Souza, Lucas Hipotálamo CRF Estresse Cardiovascular Ansiedade Hypothalamus CRF Cardiovascular Anxiety CIENCIAS BIOLOGICAS::FARMACOLOGIA CIENCIAS BIOLOGICAS::FISIOLOGIA CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA CARDIOVASCULAR |
title_short |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
title_full |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
title_fullStr |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
title_full_unstemmed |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
title_sort |
Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos |
author |
Barretto-de-Souza, Lucas |
author_facet |
Barretto-de-Souza, Lucas |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/5795792232582121 |
dc.contributor.authororcid.por.fl_str_mv |
https://orcid.org/0000-0003-1589-3297 |
dc.contributor.advisor1orcid.por.fl_str_mv |
https://orcid.org/0000-0002-1942-858X |
dc.contributor.author.fl_str_mv |
Barretto-de-Souza, Lucas |
dc.contributor.advisor1.fl_str_mv |
Crestani, Carlos Cesar |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1117432571971568 |
dc.contributor.authorID.fl_str_mv |
6228fffc-0fe8-4842-9918-1bcdf36b1ebe |
contributor_str_mv |
Crestani, Carlos Cesar |
dc.subject.por.fl_str_mv |
Hipotálamo CRF Estresse Cardiovascular Ansiedade |
topic |
Hipotálamo CRF Estresse Cardiovascular Ansiedade Hypothalamus CRF Cardiovascular Anxiety CIENCIAS BIOLOGICAS::FARMACOLOGIA CIENCIAS BIOLOGICAS::FISIOLOGIA CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA CARDIOVASCULAR |
dc.subject.eng.fl_str_mv |
Hypothalamus CRF Cardiovascular Anxiety |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FARMACOLOGIA CIENCIAS BIOLOGICAS::FISIOLOGIA CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA CARDIOVASCULAR |
description |
The lateral hypothalamus (LH) is a hypothalamic area implicated in the integration of physiological and behavioral responses to stress. Indeed, it has been demonstrated the involvement of the LH in cardiovascular responses to stress and in the control of behavioral responses related to anxiety and depression. The corticotropin-releasing factor (CRF) system has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments induced by exposure to aversive situations. In addition, chronic exposure to aversive situations affects the expression of CRF components in brain regions involved in the control of stress responses. Therefore, the hypothesis of our work was that the CRF neurotransmission present in the LH is involved in the cardiovascular and anxiety-like behavioral changes induced by acute or repeated restraint stress, as well as in the cardiovascular changes induced by chronic variable stress (CVS). Initially, we investigated the effect of bilateral microinjection of the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine-30 (ASV-30) on cardiovascular responses during acute restraint stress. It was identified that microinjection of CP376395 or ASV-30 into the LH decreased the tachycardia response during an acute session of restraint stress, but without altering the pressor responses and tail skin temperature drop. We also compared the effect of LH treatment with CRF1 or CRF2 receptor antagonists on cardiovascular responses during the 1st and 10th session of restraint stress. As observed in the acutely stressed animals, we identified that treatment of the LH with CP376395 or ASV-30 reduced the tachycardia response during the 10th restraint stress session. Furthermore, treatment of the HL with CP376395 increased the tail skin temperature drop response during the 10th restraint session. In addition, we evaluated the involvement of LH CRF1 and CRF2 receptors in the control of anxiety-like behavior induced by an acute or 10 sessions of restraint stress. We identified that treatment of the LH with CP376395 or ASV-30 inhibited the ansiogenic-like effect in the elevated plus maze (EPM) induced by the acute session of restraint stress. We did not identify behavioral changes in the EPM in animals repeatedly subjected to restraint stress, and pharmacological treatments also had no behavioral effect when administered before the 10th restraint session. The evaluation of the influence of the CRF system on the cardiovascular changes induced by CVS indicated that antagonism of either CRF1 or CRF2 receptors in the LH prevented the impairment in baroreflex activity observed in animals subjected to CVS. Finally, the effect of exposure to repeated restraint stress (RRS) or CVS on protein levels of CRF receptors in the LH was assessed. It was observed that RRS had no influence on the levels of both CRF receptors, but CVS caused an increase in CRF2 receptor protein levels, but without altering CRF1 receptor levels. In summary, the data of the present study indicate that CRF neurotransmission in the LH mediates cardiovascular and behavioral responses to acute and chronic stress. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-10-17T13:15:30Z |
dc.date.available.fl_str_mv |
2023-10-17T13:15:30Z |
dc.date.issued.fl_str_mv |
2023-09-26 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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dc.identifier.citation.fl_str_mv |
BARRETTO-DE-SOUZA, Lucas. Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos. 2023. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/ufscar/18777. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/18777 |
identifier_str_mv |
BARRETTO-DE-SOUZA, Lucas. Envolvimento da neurotransmissão do fator liberador de corticotrofina (CRF) no hipotálamo lateral nas respostas cardiovasculares e comportamentais ao estresse em ratos. 2023. Tese (Doutorado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/ufscar/18777. |
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https://repositorio.ufscar.br/handle/ufscar/18777 |
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Universidade Federal de São Carlos Câmpus São Carlos |
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Universidade Federal de São Carlos Câmpus São Carlos |
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