Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR

International Journal of Molecular Sciences

Fei Cai³  Jue Liu⁴  Cairong Li²  Jianghua Wang¹ 

[1] Fisheries College, Huazhong Agricultural University, Wuhan 430070, ChinaHubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China;Department of Pharmacology, Hubei University of Science and Technology, Xianning 437100, China;Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China;

关键词: microcystin-LR;    endoplasmic reticulum stress;    cognitive impairment;    tauroursodeoxycholic acid;   

DOI  :  10.3390/ijms161226083

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.