As consequências dos maus-tratos na infância na reprogramação neuroimunoendócrina em adolescentes saudáveis e modelo animal de separação materna

• Ano de defesa: 2016
• Autor(a) principal: Prado, Carine Hartmann do
• Orientador(a): Bauer, Moisés Evandro
• 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: Faculdade de Biociências
• País: Brasil
• Palavras-chave em Português: MAUS-TRATOS INFANTIS; SISTEMA IMUNOLÓGICO; BIOLOGIA CELULAR
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/6971

Childhood maltreatment (CM) exposure, including physical, sexual and psychological abuse, as well as physical or emotional neglect, is associated to long-term effects on mental health. The individual’s earlier years of life are characterized by rapid neurobiological and psychological development; therefore, CM is considered an important risk factor for psychological impairment and increased vulnerability to mood disorders. It is well established that alterations in the stress response systems, such as the immune and neuroendocrine systems are involved in this process. Based on this, investigating the effects of CM exposure in healthy adolescents can help to identify patterns of vulnerability to mood disorders in adulthood. The main objectives are: 1) to investigate the effects of CM exposure in neuroimunoendocrine and oxidative parameters in healthy adolescents without mood disorder; 2) to analyze early life stress effects in an animal model of maternal separation (MS) in cognitive performance, immune and oxidative parameters. The first study recruited thirty healthy adolescents reporting CM and twenty-seven healthy adolescents with no history of CM as control group. Blood, plasma and hair samples were obtained from all participants. Lymphocytes were isolated and stimulated in vitro to evaluate lymphocyte subsets, Th1/Th2/Th17 cytokines, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (Nfkb) signaling pathways as well as lymphocyte sensitivity to dexamethasone by flow cytometry. Brain-derived neurotrophic factor (BDNF) and hair cortisol were assessed with enzyme-linked immunosorbent assays (ELISA). Increased percentage of activated T cells (CD3+CD+CD25+ and CD3+CD69+) and senescent T cells (CD8+CD28- and CD4+CD28-), as well as a reduction of NK cells (CD3-CD56+), and NKT cells (CD3+CD56+) were observed in healthy adolescents exposed to CM. Also, it was observed an increase of intracellular signaling through increased phosphorylation of ERK1 / 2 and NF-B and increased cytokine production, such as IL-2, IFN-y and IL-17 following CM, suggesting increased cellular activation. Increased hair cortisol levels along with increased lymphocyte resistance to glucocorticoids in vitro, as well as low BDNF concentrations were observed in CM, reflecting the chronic stress effects on neuroendocrine parameters. The second study showed cognitive impairment, loss of parvalbumin and increased pro-inflammatory cytokines (TNF-) peripherally following MS. The intervention of the enriched environment was effective in reversing memory damage as well as inflammation caused by MS. In conclusion, our results suggest that CM alter neuroimunoendocrine and oxidative responses in both, animal and human models. Thus, the understanding of the underlying mechanisms by which CM modulates the central nervous system, endocrine, and immune system and how these systems interact to alter the physiological responses of children and healthy adolescents, may help to increase preventive actions against the development of chronic inflammatory diseases and mood disorders in adulthood.