title: Endoplasmic reticulum stress-mediated hippocampal neuron apoptosis involved in diabetic cognitive impairment.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.forename: Linhao
authors.initials: L
authors.lastname: Xu
authors.forename: Daqiang
authors.initials: D
authors.lastname: He
authors.forename: Shucai
authors.initials: S
authors.lastname: Ling
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053454:Caspase 12 / Q000378:metabolism; D002478:Cells, Cultured; D060825:Cognitive Dysfunction / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D051381:Rats; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D051742:Transcription Factor CHOP; D053454:Caspase 12