ABSTRACT
Objective To observe the effects of an enriched environment (EE) on cognitive functioning and the synaptic plasticity of mice modeling post-stroke cognitive impairment (PSCI) and explore the possible mechanisms involved.Methods Mice modeling PSCI and sham-operated mice were randomly divided into 3 groups:sham-operated mice in a standard environment (the Sham+SE group),PSCI mice in a standard environment (the PSCI+SE group) and PSCI mice in an enriched environment (the PSCI+EE group).The cognitive functioning of all of the mice was quantified using a Morris water maze and their hippocampal long-term potentiation (LTP) was recorded using an electrophysiological method.The level of synaptophysin was detected using Western blotting.Synaptic ultrastructure in the hippocampus was imaged using electron microscopy.Results Compared with the Sham +SE group,the PSCI+SE group showed significantly poorer water maze performance and failed induction of contralateral LTP.Their average level of synaptophysin was significantly lower,and significant adverse changes in the synaptic ultrastructure of the hippocampus were observed,including a decreased number of synapses.The average width of the synaptic cleft,postsynaptic density and the interface curvature of the synapses were all less desirable.All of the measurements of the PSCI+EE group improved significantly compared to those of the PSCI+SE group,but were still significantly poorer than those of the Sham+SE group.Conclusions An enhanced environment can improve the cognitive functioning of mice modelling PSCI.It may be that an EE can improve synaptic plasticity in the hippocampus contralateral to the stroke.
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 molec-ular biology methods. Results Compared with the sham group, the scores of Morris water maze test decreased in PSCI group (t>29.412, P26.227, P28.593, P24.126, P25.634, P24.704, P<0.05). Conclusion Transient MCAO could cause PSCI. The function of the central cholinergic circuits was impaired, especially the his-tone 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.