Effect of eplerenone on cognitive impairment in spontaneously hypertensive rats

Objective: The present study aimed to determine the effect of blocking brain mineralocorticoid receptor on cognitive impairment in spontaneously hypertensive rats and its intracellular changes.

Methods: 12-week-old male spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were given eplerenone (EPL, 30 mg/Kg/d or 100 mg/Kg/d) or pure water via oral gavage daily for 8 weeks. Effects of blocking brain mineralocorticoid receptor (MR) on cognitive function were examined through cognitive behavioral experiments. The morphology of hippocampal neurons was observed. Synaptic proteins and autophagy levels were detected by western blot.

Results: The results showed decreases in both short-term working memory and long-term spatial learning and memory ability, hippocampal neuron damage, and reduced expression of synaptic proteins in the SHR-Veh group. Impaired autophagy was found in the SHR-Veh group as evidenced by decreased expression levels of Beclin-1 protein and a defect in P62 degradation. These abnormalities were reversed by eplerenone, either the high dosage or low dosage. Reduced cognitive dysfunction and enhanced autophagy in hippocampal neurons in both SHR-EPL30 group and SHR-EPL100 group were independent of lowering blood pressure.

Conclusion: Eplerenone improves cognitive deficits observed in SHRs, and increases autophagy in hippocampal neurons of SHRs, which suggests a new site of MR antagonists in treatment of hypertension-related cognitive impairment.