Environmental Enrichment Improves Spatial Learning And Memory In Vascular Dementia Rats And Its Possible Mechanism

BACKGROUNDS: With the development of society ages and higher morbidity of cerebrovascular diseases,the number of patients with vascular dementia(Va D)is increasing.VaD is the second most common cause of dementia in the elderly,after Alzheimer disease(AD),which causes large social and economical burden to the human beings.To date,it is still very difficult to treat the impairment of VaD.Environmental Enrichment(EE)has been proved to have beneficial effect on some neuropsychiatric disorders.In this study,we aim to investigate whether Environmental Enrichment could improve the spatial learning and memory in rats with vascular dementia(VaD)and the mechanism underpinning it.METHODS: Bilateral common carotid occlusion(2-vessel occlusion,2VO)was used to develop the animal model of vascular dementia.Adult male Sprague-Dawley(SD)rats were included in the experiment and were randomly divided into four groups: sham group,2VO group,sham+EE group and 2VO+EE group.2VO group and 2VO+EE underwent bilateral common carotid occlusion.Two different housing conditions were used in this experiment: Standard environment(SE)and Enriched environment(EE).Rats in sham group and 2VO group were put into SE cage for four weeks while rats in sham+EE group and 2VO+EE group were put into EE cage for four weeks.Morris water maze(MWM)was used to detect the spatial learning and memory.Apoptosis was detected by TUNEL.The damage of neurons in hippocampus was assessed by Nissl staining.The level of wnt pathway proteins were detected by western blot.RESULTS:(1)Compared with 2VO group,the rats in 2VO+EE group had better behavioral performance in Morris water maze(MWM).Compared with sham group,the rats in sham+EE group also had better behavioral performance in MWM.(2)Compared with sham group,the rats in 2VO group had more apoptotic neurons,but the number of apoptotic neurons was less in 2VO+EE group than that in 2VO group,and the number of apoptotic neurons was less in sham+EE group than that in sham group.(3)Compared with sham group,the rats in 2VO group had less survival neurons,but there are more survival neurons in 2VO+EE group than that in 2VO group,and there are more survival neurons in sham+EE group than that in sham group.(4)Western blot showed that the level of wnt pathway proteins were increased in EE group(sham+EE and 2VO+EE group)than that in SE(sham and 2VO group)group.CONCLUSIONS: Environmental Enrichment could improve the spatial learning and memory,attenuate the apoptosis and increase the number of neurons in rats with vascular dementia,Its mechanism may related to the activation of wnt/?-catenin signal pathway.