Efeitos do isolamento e suporte social sobre indicadores epigenéticos e níveis de BDNF em hipocampo de ratos cronicamente estressados

• Ano de defesa: 2019
• Autor(a) principal: Borges, Juliano Viana
• Orientador(a): Bromberg, Elke
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biologia Celular e Molecular
• Departamento: Escola de Ciências
• País: Brasil
• Palavras-chave em Português: Suporte Social; Estresse; Acetilação; Metilação; Memória; BDNF
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/8854

Stress is characterized by a set of actions taken in response to situations that alter the normal physiology of the organism. When chronic, the stress leads to alteration of body homeostasis, physical and mental impairment. Social isolation has already been pointed out as a cause of stress for animal species with social conviviality characteristics. The social deprivation can induce damages to the organism, leading to changes in the Central Nervous System (CNS), which can culminate in anxiety and depression, as well as memory deficits. These CNS changes may be associated with molecular variations, such as brain-derived neurotrophic factor (BDNF), which is very important for neuronal physiology and plasticity. The support provided by social coexistence can attenuate the effects of chronic stress and social isolation, improving physical and cognitive aspects. The social isolation of adult animals still is little explored in the scientific literature, so the objective of this work was to investigate the effects of isolation and social support on: level and expression of BDNF in the hippocampus; molecular mechanisms of histones acetylation and methylation of DNA in the hippocampus; on behavioral parameters of memory and anxiety in chronically stressed adult animals, aged three and seventeen months. The exposure of three-month old animals to social isolation and chronic stress showed that social isolation was detrimental to memory, but the increase in anxiety can only be observed in animals that were isolated and submitted to the unpredictable chronic stress protocol (CUS). The weight gain during the experiment was lower in animals that were stressed by CUS. BDNF was decreased in isolated animals in comparison to accompanied groups, and HDAC5 expression was increased only in animals that were isolated and stressed. Acetylation of H4K12 was higher in the hippocampus of accompanied animals, and H3K9 was decreased in animals that were isolated and stressed. Seventeen-month old animals also had memory impaired by isolation compared to accompanied, and anxiety was lower only in animals that were accompanied and non-stressed. The weight gain during the experiment was lower in animals that were stressed by CUS. The expression of BDNF was higher in the hippocampus of accompanied animals. Expression of HDAC5 and DNMT1 were higher in animals that were isolated and stressed, whereas DNMT3a expression was indifferent to the isolation and stress protocols. In conclusion, the study showed that the social isolation of adult animals can induce epigenetic alterations and to exacerbate the effect of chronic stress in cognitive and molecular parameters, indicating that social support can be effective in attenuating some harmful effects caused by stress.