Angiotensin-(1-7) via the mas receptor alleviates the diabetes-induced decrease in GFAP and GAP-43 immunoreactivity with concomitant reduction in the COX-2 in hippocampal formation: an immunohistochemical study.
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.
Department of Anatomy, Faculty of Medicine, Kuwait University, P. O. Box 24923, Safat, 13110, Kuwait. wrenno@hsc.edu.kw
Waleed M
WM
Renno
Anwar G
AG
Al-Banaw
Preethi
P
George
Asmaa A
AA
Abu-Ghefreh
Saghir
S
Akhtar
Ibrahim F
IF
Benter
D000803:Angiotensin I / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D019922:GAP-43 Protein / Q000032:analysis / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000378:metabolism*
D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C118790:angiotensin I (1-7)