Efeitos do isolamento social, estresse crônico imprevisível e do suporte social na acetilação e metilação de histonas em hipocampo de ratos de meia idade

Detalhes bibliográficos
Autor(a) principal: Pires, Vivian Naziaseno
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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spelling 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: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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
dc.date.accessioned.fl_str_mv 2023-03-21T20:04:23Z
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