Abstract: Objective To observe the change of histone acetylation homeostasis of the central cholinergic circuits in mice with post-stroke cognitive impairment (PSCI). Methods The male ICR mice were divided into sham group (n=60) and PSCI group (n=60). The middle cerebral artery occlusion (MCAO) model was established. The Morris water maze test was used to test the cognitive function, and the changes of function and the histone acetylation homeostasis of the central cholinergic circuits of unaffected side were detected by molecular biology methods. Results Compared with the sham group, the scores of Morris water maze test decreased in PSCI group (t>29.412, P< 0.05); while the acetylcholine (Ach) level decreased (t>26.227, P<0.05), as well as the expression of choline acetyltransferase (ChAT) mRNA and protein (t>28.593, P<0.05), acetylated histone H3 (Ac-H3) (t>24.126, P<0.05), phosphorylated cAMP response element-binding protein (p-CREB) and CREB binding protein (CBP) (t>25.634, P<0.05), and the acetylated histone level of M promoter of ChAT (t>24.704, P<0.05). Conclusion Transient MCAO could cause PSCI. The function of the central cholinergic circuits was impaired, especially the histone acetylation homeostasis of the central cholinergic circuits, such as the acetylated histone level of ChAT promoter decreased. All of that might be related with the decline of p-CREB and CBP level in the corresponding brain regions induced by stroke.

Key words: post-stroke cognitive impairment, cholinergic circuits, acetylcholine, histone acetylation, cAMP response element-binding