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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Vasopressin Impairment During Sepsis Is Associated with Hypothalamic Intrinsic Apoptotic Pathway and Microglial Activation

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Autor(es):
Angenendt da Costa, Luis Henrique ; dos Santos Junior, Nilton Nascimento ; Rocha Catalao, Carlos Henrique ; Sharshar, Tarek ; Chretien, Fabrice ; Alves da Rocha, Maria Jose
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: Molecular Neurobiology; v. 54, n. 7, p. 5526-5533, SEP 2017.
Citações Web of Science: 4
Resumo

Previous studies have shown that in the early phase of sepsis, the plasma concentration of arginine vasopressin (AVP) is increased, but in the late phase, its levels remain inadequately low, despite of persistent hypotension. One hypothesis suggested for this relative deficiency is apoptosis of vasopressinergic neurons. Here, we investigated apoptosis pathways in the hypothalamus during sepsis, as well as mechanisms underlying this process. Male Wistar rats were submitted to sepsis by cecal ligation and puncture (CLP) or nonmanipulated (naive) as control. After 6 and 24 h, the animals were decapitated and brain and blood were collected to assess hypothalamic apoptotic markers, IFN-gamma plasma levels, and evidence for breakdown of the blood-brain barrier (BBB). Sepsis caused a decrease in mitochondrial antiapoptotic proteins (Bcl-2, Bcl-xL) in the hypothalamus, but had no effect on markers of cell death mediated by death receptors or immune cells. In the supraoptic nuclei of these animals, microglia morphology was consistent with activation, associated with an increase in plasma IFN-gamma. A transitory breakdown of BBB in the hypothalamus was seen at 6 h following CLP. The results indicate that the intrinsic but not extrinsic apoptosis pathway is involved in the cell death observed in vasopressinergic neurons, and that this condition is temporally associated with microglial activation and BBB leaking. (AU)

Processo FAPESP: 13/03723-3 - Avaliação do comprometimento neuronal hipotalâmico na secreção de vasopresina durante a sepse
Beneficiário:Luís Henrique Angenendt da Costa
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 12/22246-9 - Alterações neuroimunoendócrinas no eixo hipotálamo-neurohipófise durante sepse experimental
Beneficiário:Maria José Alves da Rocha
Linha de fomento: Auxílio à Pesquisa - Regular