Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR
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-in...
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| Format: | Online |
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MDPI
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691030/ |
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pubmed-46910302016-01-06 Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR Cai, Fei Liu, Jue Li, Cairong Wang, Jianghua Article 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. MDPI 2015-11-25 /pmc/articles/PMC4691030/ /pubmed/26602924 http://dx.doi.org/10.3390/ijms161226083 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Cai, Fei Liu, Jue Li, Cairong Wang, Jianghua |
| spellingShingle |
Cai, Fei Liu, Jue Li, Cairong Wang, Jianghua Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR |
| author_facet |
Cai, Fei Liu, Jue Li, Cairong Wang, Jianghua |
| author_sort |
Cai, Fei |
| title |
Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR |
| title_short |
Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR |
| title_full |
Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR |
| title_fullStr |
Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR |
| title_full_unstemmed |
Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR |
| title_sort |
critical role of endoplasmic reticulum stress in cognitive impairment induced by microcystin-lr |
| description |
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. |
| publisher |
MDPI |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691030/ |
| _version_ |
1613516729356386304 |