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

Author(s)

Angenendt da Costa, Luis Henrique ; dos Santos Junior, Nilton Nascimento ; Rocha Catalao, Carlos Henrique ; Sharshar, Tarek ; Chretien, Fabrice ; Alves da Rocha, Maria Jose

• Document type: Journal article
• Source: Molecular Neurobiology; v. 54, n. 7, p. 5526-5533, SEP 2017.
• Web of Science Citations: 4

Abstract

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)

• FAPESP's process: 13/03723-3 - Evaluation of hypotalamic neuronal impairment in vasopressin secretion during sepsis
• Grantee: Luís Henrique Angenendt da Costa
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/22246-9 - Neuroimmunoendocrine alteration in the hypothalamus-hypophysis axis during experimental sepsis
• Grantee: Maria José Alves da Rocha
• Support Opportunities: Regular Research Grants