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Neuroimmunoendocrine alteration in the hypothalamus-hypophysis axis during experimental sepsis

Grant number: 12/22246-9
Support Opportunities:Regular Research Grants
Duration: May 01, 2013 - October 31, 2015
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Maria José Alves da Rocha
Grantee:Maria José Alves da Rocha
Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers:Fazal Wahab


Clinical and experimental studies report that in the early phase of sepsis occurs an increase of vasopressin secretion but in the late phase, despite the high decrease of arterial pressure the hormone plasma concentrations remain inadequately low, contributing for the hypotension, shock and death.One of the suggested hypotheses for this relative deficiency of AVP is the excessive production of cytokines including IL-1² that would induce the NO production systemically and in the central nervous system causing oxidative stress and hypothalamic neuronal apoptosis affecting the synthesis and/or secretion of the hormone. Our group observed that in fact during experimental sepsis occurs a decrease of AVP mRNA and increase in the NO inducible enzyme (iNOS) in the supraoptic and paraventricular nuclei. Evidence of oxidative stress was observed in these nuclei by the increase of cleaved caspase 3, HIF-1 alfa and changes in the localization pattern of cytochrome C and apoptosis in some neurons. Additionally we observed an increase of IL-1² e IL-1R1 mainly in the supraoptic nucleus, but we did not prove the involvement of this cytokines in the central production of NO, mithocondrial oxidative stress and neuronal apoptosis in vasopressinergic neurons. Recently was reported that the vasopressinergic neurons are particularly sensitive to the cytotoxic lymphocytes CD8+ (LT-CD8+) infiltrated in the supraoptic and paraventricular hypothalamic nuclei during induced acute encephalomyelitis in mice. The animals that survived to encephalomyelitis had central Diabetes Insipidus and its magnocelular neurons showed an upregulation of MHC class I molecules in response to IFN- ³ production by the pathogenic CD 8 T cells. If these alterations can also happen during sepsis is unknown.The aim of this project is to analyze the neuroimmunoendocrine changes in the hypothalamus-neurohypophysis axis during experimental sepsis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANGENENDT DA COSTA, LUIS HENRIQUE; DOS SANTOS JUNIOR, NILTON NASCIMENTO; ROCHA CATALAO, CARLOS HENRIQUE; SHARSHAR, TAREK; CHRETIEN, FABRICE; ALVES DA ROCHA, MARIA JOSE. Vasopressin Impairment During Sepsis Is Associated with Hypothalamic Intrinsic Apoptotic Pathway and Microglial Activation. Molecular Neurobiology, v. 54, n. 7, p. 5526-5533, . (13/03723-3, 12/22246-9)

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