Abstract: Objective To 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.
Methods Forty 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. Results Compared 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. Conclusion Ang(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.