Effects of angiotensin-(1-7) on hippocampal expressions of GFAP and GDNF and cognitive function in rats with diabetes mellitus.
- Author:
Dongling ZHANG
1
;
Qian XIAO
;
Huiqiong LUO
;
Kexiang ZHAO
Author Information
- Publication Type:Journal Article
- MeSH: Angiotensin I; pharmacology; Animals; Astrocytes; Caspase 3; metabolism; Cognition; Cognition Disorders; Diabetes Mellitus, Experimental; physiopathology; Glial Cell Line-Derived Neurotrophic Factor; metabolism; Glial Fibrillary Acidic Protein; metabolism; Hippocampus; cytology; metabolism; Male; Memory; Neurons; Peptide Fragments; pharmacology; Rats; Rats, Sprague-Dawley; Streptozocin
- From: Journal of Southern Medical University 2015;35(5):646-651
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effects of angiotensin-(1-7) on the learning and memory abilities and the expressions of glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus of diabetic rats.
METHODSForty male SD rats were randomly assigned into 4 groups, namely the control group, diabetic group, Ang(1-7)-treated diabetic group (DM1 group), and Ang-(1-7)- and Mas receptor antagonist A779-treated diabetic group (DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (60 mg/kg). The cognitive function of the rats was assessed with Morris water maze (MWM) test. The expressions of GDNF in the hippocampus were examined by RT-PCR and Western blot. Nissl staining was performed to evaluate the morphological changes in rat hippocampus. The expressions of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and caspase-3 were measured by immunohistochemistry.
RESULTSCompared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities (P<0.05) with lowered expression of GDNF and increased caspase-3 expression in the hippocampus (P<0.05) and significant hippocampal neuronal and astrocyte injuries (P<0.05). Treatment with Ang(1-7) obviously improved the learning and memory abilities of the diabetic rats (P<0.05), increased GDNF and GFAP expressions (P<0.05), lowered caspase-3 expression (P<0.05), and increased the number of surviving neurons in the hippocampus (P<0.05). Such effects of Ang(1-7) effect was blocked by treatment with A779 of the diabetic rats.
CONCLUSIONAng(1-7) can alleviate cognitive dysfunction in diabetic rats possibly by up-regulating the expressions of GFAP and GDNF and promoting neuron survival in the hippocampus.