Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | https://tede2.pucrs.br/tede2/handle/tede/10664 |
Resumo: | Studies suggest that social isolation is a potent stressor for social individuals, triggering physiological changes in the stress response, making the individual more vulnerable. Chronic Unpredictable Stress (CUS) is characterized by alternating different types of stressors at different times, causing behavioral, physiological and epigenetic changes. However, social support has been studied as a potential intervention to mitigate the negative effects of stressors. The alteration of histone acetylation and methylation patterns in middle-aged animals under adverse conditions shows consequences in the transcription of essential factors for the maintenance of the individuals homeostasis. The present study aimed to analyze the effects of social isolation, unpredictable chronic stress and social buffering on epigenetic mechanisms potentially involved in the modulation of neural plasticity in the hippocampus of middle-aged rats. Therefore, male Wistar rats (17 months of age, n=46) were divided into four experimental groups: Isolated (one animal per housing box), Stressed isolates (one animal per housing box subjected to daily stress), Accompanied (2 animals per housing crate) and Stressed Accompanied (two animals per housing crate, but only one of them was subjected to daily stress). Stressed animals were submitted to a CUS protocol for 30 days. The isolated and monitored animals without stress remained in their dwelling boxes for the same period. The hippocampus was collected and the acetylation and methylation of H3K9 and methylation of H3K27 were evaluated by Western Blotting and the corticosterone in the hair was analyzed by LC-MS/MS. Isolation decreased corticosterone levels and acetylation of H3K9, in addition to increasing its methylation levels. CUS also decreases H3K9 acetylation, in addition to increasing H3K27 methylation. There was also an interaction between the effects of housing type and treatment with the UHC protocol, so that the lowest levels of corticosterone were recorded for the animals isolated and submitted to UHC. Thus, it is concluded that social isolation in middle-aged animals is capable of inducing epigenetic changes potentially involved in the regulation of modulating factors, plasticity and neuronal survival. Additionally, this study also provides evidence that social support is able to buffer the negative effects of UHC on the HPA axis. |
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Bromberg, Elkehttp://lattes.cnpq.br/5994046237491735http://lattes.cnpq.br/7423151614233196Pires, Vivian Naziaseno2023-03-21T20:04:23Z2022-03-28https://tede2.pucrs.br/tede2/handle/tede/10664Studies suggest that social isolation is a potent stressor for social individuals, triggering physiological changes in the stress response, making the individual more vulnerable. Chronic Unpredictable Stress (CUS) is characterized by alternating different types of stressors at different times, causing behavioral, physiological and epigenetic changes. However, social support has been studied as a potential intervention to mitigate the negative effects of stressors. The alteration of histone acetylation and methylation patterns in middle-aged animals under adverse conditions shows consequences in the transcription of essential factors for the maintenance of the individuals homeostasis. The present study aimed to analyze the effects of social isolation, unpredictable chronic stress and social buffering on epigenetic mechanisms potentially involved in the modulation of neural plasticity in the hippocampus of middle-aged rats. Therefore, male Wistar rats (17 months of age, n=46) were divided into four experimental groups: Isolated (one animal per housing box), Stressed isolates (one animal per housing box subjected to daily stress), Accompanied (2 animals per housing crate) and Stressed Accompanied (two animals per housing crate, but only one of them was subjected to daily stress). Stressed animals were submitted to a CUS protocol for 30 days. The isolated and monitored animals without stress remained in their dwelling boxes for the same period. The hippocampus was collected and the acetylation and methylation of H3K9 and methylation of H3K27 were evaluated by Western Blotting and the corticosterone in the hair was analyzed by LC-MS/MS. Isolation decreased corticosterone levels and acetylation of H3K9, in addition to increasing its methylation levels. CUS also decreases H3K9 acetylation, in addition to increasing H3K27 methylation. There was also an interaction between the effects of housing type and treatment with the UHC protocol, so that the lowest levels of corticosterone were recorded for the animals isolated and submitted to UHC. Thus, it is concluded that social isolation in middle-aged animals is capable of inducing epigenetic changes potentially involved in the regulation of modulating factors, plasticity and neuronal survival. Additionally, this study also provides evidence that social support is able to buffer the negative effects of UHC on the HPA axis.Estudos sugerem que o isolamento social é um potente estressor para indivíduos sociais desencadeando alterações fisiológicas na resposta ao estresse tornando o indivíduo mais vulnerável. O estresse crônico imprevisível (CUS, do inglês, Chronic Unpredictable Stress) caracteriza-se por alternar diferentes tipos de estressores em horários variados, provocando alterações comportamentais, fisiológicas e epigenéticas. Entretanto, o suporte social vem sendo estudado como uma forma de mitigar os efeitos de estressores. A alteração dos padrões de acetilação e metilação de histonas de animais de meia idade em condições adversas mostra consequências na transcrição de fatores essenciais para a manutenção da homeostase do indivíduo. O presente estudo teve como objetivo analisar os efeitos do isolamento social, do estresse crônico imprevisível e do tamponamento social sobre mecanismos epigenéticos potencialmente envolvidos na modulação da plasticidade neural em hipocampo de ratos de meia idade. Para tanto, ratos Wistar machos (17 meses de idade, n=46) foram divididos em quatro grupos experimentais: Isolados (um animal por caixa moradia), Isolados estressados (uma animal por caixa moradia submetido a estresse diário), Acompanhados (2 animais por caixa moradia) e Acompanhados estressados (dois animais por caixa moradia, mas apenas um deles era submetido a estresse diário). Os animais estressados foram submetidos, durante 30 dias, a um protocolo de CUS. Os animais isolados e acompanhados sem estresse permaneceram em suas caixas moradias pelo mesmo período. O hipocampo foi coletado e a acetilação e metilação de H3K9 e metilação da H3K27 foram avaliadas por Western Blotting e a corticosterona no pelo foi analisada por LC-MS/MS. O isolamento diminuiu os níveis de corticosterona e a acetilação da H3K9, além de aumentar seus níveis de metilação. O CUS também diminui a acetilação da H3K9, além de aumentar a metilação da H3K27. Observou-se ainda uma interação entre os efeitos do tipo de alojamento e o tratamento com o protocolo de CUS, de modo que os níveis mais baixos de corticosterona foram registrados para os animais isolados e submetidos ao CUS. Desta forma, conclui-se que o isolamento social em animais de meia idade é capaz de induzir alterações epigenéticas potencialmente envolvidas na regulação de fatores moduladores plasticidade e sobrevivência neuronal. Adicionalmente, este estudo também traz evidências de que o suporte social é capaz de tamponar os efeitos negativos do CUS sobre o eixo HPA.Submitted by PPG Gerontologia Biomédica (geronbio@pucrs.br) on 2023-03-14T18:20:05Z No. of bitstreams: 1 Dissertação_Vivian Naziaseno Pires.pdf: 1953996 bytes, checksum: f7fdafb5b6ef7bc91f66c04b500a64f3 (MD5)Approved for entry into archive by Sarajane Pan (sarajane.pan@pucrs.br) on 2023-03-21T19:46:07Z (GMT) No. of bitstreams: 1 Dissertação_Vivian Naziaseno Pires.pdf: 1953996 bytes, checksum: f7fdafb5b6ef7bc91f66c04b500a64f3 (MD5)Made available in DSpace on 2023-03-21T20:04:23Z (GMT). No. of bitstreams: 1 Dissertação_Vivian Naziaseno Pires.pdf: 1953996 bytes, checksum: f7fdafb5b6ef7bc91f66c04b500a64f3 (MD5) Previous issue date: 2022-03-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttps://tede2.pucrs.br/tede2/retrieve/186768/DIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Gerontologia BiomédicaPUCRSBrasilInstituto de Geriatria e GerontologiaEpigenéticaEstresse CrônicoHistonasH3K9ackH3K9meK3K27meCorticosteronaTamponamento SocialEpigeneticsChronic StressHistonesH3K9ackH3K9mK3K27meCorticosteroneSocial BufferingCIENCIAS DA SAUDE::MEDICINAEfeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idadeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTrabalho será publicado como artigo ou livro60 meses21/03/202889696450708863641605005005006002296420844541114010-9693694523087866273590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILDIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.jpgDIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.jpgimage/jpeg4093https://tede2.pucrs.br/tede2/bitstream/tede/10664/4/DIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.jpg0e563b07c6dfc35ffba130a9b215e55fMD54TEXTDIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.txtDIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.txttext/plain2273https://tede2.pucrs.br/tede2/bitstream/tede/10664/3/DIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf.txt91b09a9532629472de46c7710eda22c5MD53ORIGINALDIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdfDIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdfapplication/pdf723284https://tede2.pucrs.br/tede2/bitstream/tede/10664/2/DIS_VIVIAN_NAZIASENO_PIRES_CONFIDENCIAL.pdf11f1e8512b4f06f3a1e5d7640295d320MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590https://tede2.pucrs.br/tede2/bitstream/tede/10664/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/106642023-03-21 20:00:15.231oai:tede2.pucrs.br:tede/10664QXV0b3JpemE/P28gcGFyYSBQdWJsaWNhPz9vIEVsZXRyP25pY2E6IENvbSBiYXNlIG5vIGRpc3Bvc3RvIG5hIExlaSBGZWRlcmFsIG4/OS42MTAsIGRlIDE5IGRlIGZldmVyZWlybyBkZSAxOTk4LCBvIGF1dG9yIEFVVE9SSVpBIGEgcHVibGljYT8/byBlbGV0cj9uaWNhIGRhIHByZXNlbnRlIG9icmEgbm8gYWNlcnZvIGRhIEJpYmxpb3RlY2EgRGlnaXRhbCBkYSBQb250aWY/Y2lhIFVuaXZlcnNpZGFkZSBDYXQ/bGljYSBkbyBSaW8gR3JhbmRlIGRvIFN1bCwgc2VkaWFkYSBhIEF2LiBJcGlyYW5nYSA2NjgxLCBQb3J0byBBbGVncmUsIFJpbyBHcmFuZGUgZG8gU3VsLCBjb20gcmVnaXN0cm8gZGUgQ05QSiA4ODYzMDQxMzAwMDItODEgYmVtIGNvbW8gZW0gb3V0cmFzIGJpYmxpb3RlY2FzIGRpZ2l0YWlzLCBuYWNpb25haXMgZSBpbnRlcm5hY2lvbmFpcywgY29ucz9yY2lvcyBlIHJlZGVzID9zIHF1YWlzIGEgYmlibGlvdGVjYSBkYSBQVUNSUyBwb3NzYSBhIHZpciBwYXJ0aWNpcGFyLCBzZW0gP251cyBhbHVzaXZvIGFvcyBkaXJlaXRvcyBhdXRvcmFpcywgYSB0P3R1bG8gZGUgZGl2dWxnYT8/byBkYSBwcm9kdT8/byBjaWVudD9maWNhLgo=Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2023-03-21T23:00:15Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
title |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
spellingShingle |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade Pires, Vivian Naziaseno Epigenética Estresse Crônico Histonas H3K9ack H3K9me K3K27me Corticosterona Tamponamento Social Epigenetics Chronic Stress Histones H3K9ack H3K9m K3K27me Corticosterone Social Buffering CIENCIAS DA SAUDE::MEDICINA |
title_short |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
title_full |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
title_fullStr |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
title_full_unstemmed |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
title_sort |
Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade |
author |
Pires, Vivian Naziaseno |
author_facet |
Pires, Vivian Naziaseno |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bromberg, Elke |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5994046237491735 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7423151614233196 |
dc.contributor.author.fl_str_mv |
Pires, Vivian Naziaseno |
contributor_str_mv |
Bromberg, Elke |
dc.subject.por.fl_str_mv |
Epigenética Estresse Crônico Histonas H3K9ack H3K9me K3K27me Corticosterona Tamponamento Social |
topic |
Epigenética Estresse Crônico Histonas H3K9ack H3K9me K3K27me Corticosterona Tamponamento Social Epigenetics Chronic Stress Histones H3K9ack H3K9m K3K27me Corticosterone Social Buffering CIENCIAS DA SAUDE::MEDICINA |
dc.subject.eng.fl_str_mv |
Epigenetics Chronic Stress Histones H3K9ack H3K9m K3K27me Corticosterone Social Buffering |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA |
description |
Studies suggest that social isolation is a potent stressor for social individuals, triggering physiological changes in the stress response, making the individual more vulnerable. Chronic Unpredictable Stress (CUS) is characterized by alternating different types of stressors at different times, causing behavioral, physiological and epigenetic changes. However, social support has been studied as a potential intervention to mitigate the negative effects of stressors. The alteration of histone acetylation and methylation patterns in middle-aged animals under adverse conditions shows consequences in the transcription of essential factors for the maintenance of the individuals homeostasis. The present study aimed to analyze the effects of social isolation, unpredictable chronic stress and social buffering on epigenetic mechanisms potentially involved in the modulation of neural plasticity in the hippocampus of middle-aged rats. Therefore, male Wistar rats (17 months of age, n=46) were divided into four experimental groups: Isolated (one animal per housing box), Stressed isolates (one animal per housing box subjected to daily stress), Accompanied (2 animals per housing crate) and Stressed Accompanied (two animals per housing crate, but only one of them was subjected to daily stress). Stressed animals were submitted to a CUS protocol for 30 days. The isolated and monitored animals without stress remained in their dwelling boxes for the same period. The hippocampus was collected and the acetylation and methylation of H3K9 and methylation of H3K27 were evaluated by Western Blotting and the corticosterone in the hair was analyzed by LC-MS/MS. Isolation decreased corticosterone levels and acetylation of H3K9, in addition to increasing its methylation levels. CUS also decreases H3K9 acetylation, in addition to increasing H3K27 methylation. There was also an interaction between the effects of housing type and treatment with the UHC protocol, so that the lowest levels of corticosterone were recorded for the animals isolated and submitted to UHC. Thus, it is concluded that social isolation in middle-aged animals is capable of inducing epigenetic changes potentially involved in the regulation of modulating factors, plasticity and neuronal survival. Additionally, this study also provides evidence that social support is able to buffer the negative effects of UHC on the HPA axis. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022-03-28 |
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2023-03-21T20:04:23Z |
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https://tede2.pucrs.br/tede2/handle/tede/10664 |
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https://tede2.pucrs.br/tede2/handle/tede/10664 |
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por |
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por |
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8969645070886364160 |
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500 500 500 600 |
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2296420844541114010 |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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PUCRS |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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