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Cell Mol Neurobiol ; 32(8): 1323-36, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22711212

RESUMO

We have previously shown that chronic treatment with angiotensin-(1-7) [Ang-(1-7)] can prevent diabetes-induced cardiovascular dysfunction. However, effect of Ang-(1-7) treatment on diabetes-induced alterations in the CNS is unknown. The aim of this study was to test the hypothesis that treatment with Ang-(1-7) can produce protection against diabetes-induced CNS changes. We examined the effect of Ang-(1-7) on the number of cyclooxygenase-2 (COX-2) immunoreactive neurons and the glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes and assessed the changes in the neuronal growth-associated protein-43 (GAP-43) of the hippocampal formation in streptozotocin-induced diabetes in rats. Animals were sacrificed 30 days after induction of diabetes and/or treatment with Ang-(1-7). Ang-(1-7) treatment significantly prevented diabetes-induced decrease in the number of GFAP immunoreactive astrocytes and GAP-43 positive neurons in all hippocampal regions. Co-administration of A779, a selective Ang-(1-7) receptor antagonist, inhibited Ang-(1-7)-mediated protective effects indicating that Ang-(1-7) produces its effects through activation of receptor Mas. Further, Ang-(1-7) treatment through activation of Mas significantly prevented diabetes-induced increase in the number of the COX-2 immunolabeled neurons in all sub-regions of the hippocampus examined. These results show that Ang-(1-7) has a protective role against diabetes-induced changes in the CNS.


Assuntos
Angiotensina I/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Proteína GAP-43/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Angiotensina I/farmacologia , Animais , Ciclo-Oxigenase 2/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Proteína GAP-43/análise , Proteína Glial Fibrilar Ácida/análise , Hipocampo/química , Hipocampo/efeitos dos fármacos , Masculino , Fragmentos de Peptídeos/farmacologia , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/análise , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/análise
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