Department of Anatomy and Cell Biology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
Biomed Res Int. 2013;2013:924327. doi: 10.1155/2013/924327. Epub 2013 Apr 24.
Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP), the prominent mediator of the endoplasmic reticulum (ER) stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ-) induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P < 0.05). The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P < 0.05). The present results suggested that the CHOP-dependent endoplasmic reticulum (ER) stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.
糖尿病（DM）管理不善可导致认知障碍，但其机制尚未确定。本研究旨在探讨 C/EBP 同源蛋白（CHOP）的激活，该蛋白是内质网（ER）应激诱导的细胞凋亡的主要介质，在高血糖状态下。我们采用链脲佐菌素（STZ）诱导的糖尿病大鼠，通过 Morris 水迷宫试验来探讨学习和记忆能力。采用透射电子显微镜和扫描电子显微镜观察糖尿病大鼠海马区的超微结构和高糖培养基中培养的神经元。TUNEL 染色法评估细胞凋亡情况，免疫组织化学和 Western blot 检测这些海马神经元中 CHOP 的表达。糖尿病诱导 6 周后，糖尿病大鼠的逃避潜伏期延长，找到平台的平均频率降低（P < 0.05）。神经元形态和突触结构受损；糖尿病大鼠海马区和高糖培养基培养神经元中 TUNEL 阳性细胞数和 CHOP 表达明显改变（P < 0.05）。本研究结果表明，CHOP 依赖性内质网（ER）应激介导的细胞凋亡可能参与了高血糖诱导的海马突触和神经元损伤，并促进了糖尿病认知障碍的发生。
