title: Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR.
abstract: Recent studies showed that cyanobacteria-derived microcystin-leucine-arginine (MCLR) can cause hippocampal pathological damage and trigger cognitive impairment; but the underlying mechanisms have not been well understood. The objective of the present study was to investigate the mechanism of MCLR-induced cognitive deficit; with a focus on endoplasmic reticulum (ER) stress. The Morris water maze test and electrophysiological study demonstrated that MCLR caused spatial memory injury in male Wistar rats; which could be inhibited by ER stress blocker; tauroursodeoxycholic acid (TUDCA). Meanwhile; real-time polymerase chain reaction (real-time PCR) and immunohistochemistry demonstrated that the expression level of the 78-kDa glucose-regulated protein (GRP78); C/EBP homologous protein (CHOP) and caspase 12 were significantly up-regulated. These effects were rescued by co-administration of TUDCA. In agreement with this; we also observed that treatment of rats with TUDCA blocked the alterations in ER ultrastructure and apoptotic cell death in CA1 neurons from rats exposed to MCLR. Taken together; the present results suggested that ER stress plays an important role in potential memory impairments in rats treated with MCLR; and amelioration of ER stress may serve as a novel strategy to alleviate damaged cognitive function triggered by MCLR.
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, Xianning 437100, China. cf@mail.hbust.com.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China. whzxyy1880@zxhospital.com.
authors.forename: Jue
authors.initials: J
authors.lastname: Liu
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China. lcr@mail.hbust.com.cn.
authors.forename: Cairong
authors.initials: C
authors.lastname: Li
authors.affiliation: Fisheries College, Huazhong Agricultural University, Wuhan 430070, China. wangjianghua@mail.hzau.edu.cn.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008387:Marine Toxins; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D052998:Microcystins / Q000009:adverse effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats
chemical_list: D008387:Marine Toxins; D052998:Microcystins; C057862:cyanoginosin LR
keywords: cognitive impairment; endoplasmic reticulum stress; microcystin-LR; tauroursodeoxycholic acid