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环境富集通过激活Wnt/β-连环蛋白信号通路改善血管性痴呆大鼠的空间学习和记忆能力。

Environmental Enrichment Improves Spatial Learning and Memory in Vascular Dementia Rats with Activation of Wnt/β-Catenin Signal Pathway.

作者信息

Jin Xinhao, Li Tao, Zhang Lina, Ma Jingxi, Yu Lehua, Li Changqing, Niu Lingchuan

机构信息

Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).

Department of Orthopedics, The General Hospital of Chonggang, Chongqing, China (mainland).

出版信息

Med Sci Monit. 2017 Jan 13;23:207-215. doi: 10.12659/msm.902728.

Abstract

BACKGROUND Environmental enrichment (EE) has a beneficial effect on some neuropsychiatric disorders. In this study, we aimed to investigate whether environmental enrichment could improve the spatial learning and memory in rats with vascular dementia (VaD) and the mechanism underpinning it. MATERIAL AND 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 used in the experiment and were randomly divided into 4 groups: sham group, 2VO group, sham+EE group, and 2VO+EE group (n=19/group). The 2VO group and 2VO+EE group underwent bilateral common carotid occlusion. Two different housing conditions were used in this experiment: standard environment (SE) and enriched environment (EE). Rats in the sham group and 2VO group were put into SE cages for 4 weeks, while rats in the sham+EE group and 2VO+EE group were put in EE cages for 4 weeks. The Morris water maze and Y-maze were used to assess spatial learning and memory. Apoptosis was detected by TUNEL. The damage of neurons in the hippocampus was assessed by Nissl staining. The level of wnt pathway proteins were detected by Western blot. RESULTS Compared with the 2VO group, the rats in the 2VO+EE group had better behavioral performance, fewer apoptotic neurons, and more surviving neurons. Western blot analysis showed that the levels of wnt pathway proteins were higher in 2VO+EE rats than in the 2VO group. CONCLUSIONS Environmental enrichment can improve the spatial learning and memory in rats with vascular dementia, and the mechanism may be related to activation of the wnt/β-catenin signal pathway.

摘要

背景 环境富集(EE)对某些神经精神疾病具有有益作用。在本研究中,我们旨在探讨环境富集是否能改善血管性痴呆(VaD)大鼠的空间学习和记忆能力及其潜在机制。

材料与方法 采用双侧颈总动脉闭塞(双血管闭塞[2VO])法建立血管性痴呆动物模型。实验选用成年雄性Sprague-Dawley(SD)大鼠,随机分为4组:假手术组、2VO组、假手术+EE组和2VO+EE组(每组n = 19)。2VO组和2VO+EE组进行双侧颈总动脉闭塞。本实验采用两种不同的饲养条件:标准环境(SE)和富集环境(EE)。假手术组和2VO组的大鼠置于SE笼中4周,而假手术+EE组和2VO+EE组的大鼠置于EE笼中4周。采用Morris水迷宫和Y迷宫评估空间学习和记忆能力。通过TUNEL检测细胞凋亡。通过尼氏染色评估海马神经元的损伤情况。通过蛋白质印迹法检测wnt通路蛋白的水平。

结果 与2VO组相比,2VO+EE组大鼠的行为表现更好,凋亡神经元更少,存活神经元更多。蛋白质印迹分析显示,2VO+EE组大鼠的wnt通路蛋白水平高于2VO组。

结论 环境富集可改善血管性痴呆大鼠的空间学习和记忆能力,其机制可能与激活wnt/β-连环蛋白信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2a3/5253348/5426bc45b597/medscimonit-23-207-g001.jpg

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