Icariin promotes histone acetylation and attenuates post-stroke cognitive impairment in the central cholinergic circuits of mice

Abstract

Post-stroke dementia (PSD) is a common clinical disease and the central cholinergic circuits are important to cognitive function. Icariin (ICA), a flavonoid isolated from Herba Epimedii, was reported to improve cognitive function through modulating the cholinergic system. But there were no studies exploring the role of ICA in PSD animal models. In this study, we used transient middle cerebral artery occlusion mice with cognitive dysfunction in the PSD model. PSD mice were then randomly divided into six groups: Sham-operated+placebo group, Sham-operated+ICA group (60mg/kg), PSD model+placebo group, PSD model+ICA group (30, 60, or 120mg/kg). We observed spatial learning ability and memory by Morris water maze test. The levels of acetylcholine (ACH) and choline acetyltransferase (ChAT), the degree of histone acetylation and the cAMP response element-binding protein (CREB) phosphorylation in the central cholinergic circuits were investigated by Western blot and immunofluorescence. After the administration of various doses of ICA, the escape latency and searching distance of the PSD mice were reduced significantly compared with those without ICA treatment. While the levels of ACH and ChAT declined, the degree of histone acetylation and the CREB phosphorylation was improved in a dose-dependent manner in central cholinergic circuits. In conclusion, ICA can improve post-stroke dementia, and the mechanism is likely to enhance CREB phosphorylation in the central cholinergic circuits, thus improving the damage in cholinergic circuits histone acetylation homeostasis.