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Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress

Methamphetamine (MA), an illicit drug abused worldwide, leads to cognitive impairment and memory loss. However, the detailed mechanisms of MA-induced neurologic impairment are still unclear. The present study aimed to investigate the mechanisms of MA-induced inhibition of memory acquisition from the...

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Autores principales: Chen, Guang, Wei, Xiaoning, Xu, Xiang, Yu, Gang, Yong, Zheng, Su, Ruibin, Tao, Luyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840888/
https://www.ncbi.nlm.nih.gov/pubmed/33519373
http://dx.doi.org/10.3389/fnins.2020.630713
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author Chen, Guang
Wei, Xiaoning
Xu, Xiang
Yu, Gang
Yong, Zheng
Su, Ruibin
Tao, Luyang
author_facet Chen, Guang
Wei, Xiaoning
Xu, Xiang
Yu, Gang
Yong, Zheng
Su, Ruibin
Tao, Luyang
author_sort Chen, Guang
collection PubMed
description Methamphetamine (MA), an illicit drug abused worldwide, leads to cognitive impairment and memory loss. However, the detailed mechanisms of MA-induced neurologic impairment are still unclear. The present study aimed to investigate the mechanisms of MA-induced inhibition of memory acquisition from the perspective of endoplasmic reticulum (ER) stress. ER stress, caused by the accumulation of wrongly folded proteins in the ER, is important for new protein synthesis, which further influence the formation of long-term memory. A subacute MA poisoning model of mice was established and several behavioral experiments were performed, including elevated plus maze, Morris water maze, electro-stimulus Y-maze, and novel object recognition tasks. The present results suggested that 4 days exposure to MA induced significant memory loss. Whereas, this damage to memory formation could be protected when mice were pre-treated with ER stress inhibitor, tauroursodeoxycholic acid (TUDCA). The results of Western blotting showed that subacute exposure to MA increased the expression levels of ER stress marker proteins, such as binding immunoglobulin protein, phosphorylated eukaryotic translation initiation factor 2α, cyclic AMP-dependent transcription factor (ATF)-4, ATF-6, and CCAAT-enhancer binding protein homologous protein. Meanwhile, the enhanced expression levels of these proteins were reversed by TUDCA, indicating that MA administration induced memory loss by evoking ER stress in the hippocampus. We also found that MA inhibited the induction of long-term potentiation (LTP) in the hippocampus. Nevertheless, LTP could be induced when mice were pre-treated with TUDCA. In conclusion, MA inhibited long-term memory acquisition and synaptic plasticity via ER stress.
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spelling pubmed-78408882021-01-29 Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress Chen, Guang Wei, Xiaoning Xu, Xiang Yu, Gang Yong, Zheng Su, Ruibin Tao, Luyang Front Neurosci Neuroscience Methamphetamine (MA), an illicit drug abused worldwide, leads to cognitive impairment and memory loss. However, the detailed mechanisms of MA-induced neurologic impairment are still unclear. The present study aimed to investigate the mechanisms of MA-induced inhibition of memory acquisition from the perspective of endoplasmic reticulum (ER) stress. ER stress, caused by the accumulation of wrongly folded proteins in the ER, is important for new protein synthesis, which further influence the formation of long-term memory. A subacute MA poisoning model of mice was established and several behavioral experiments were performed, including elevated plus maze, Morris water maze, electro-stimulus Y-maze, and novel object recognition tasks. The present results suggested that 4 days exposure to MA induced significant memory loss. Whereas, this damage to memory formation could be protected when mice were pre-treated with ER stress inhibitor, tauroursodeoxycholic acid (TUDCA). The results of Western blotting showed that subacute exposure to MA increased the expression levels of ER stress marker proteins, such as binding immunoglobulin protein, phosphorylated eukaryotic translation initiation factor 2α, cyclic AMP-dependent transcription factor (ATF)-4, ATF-6, and CCAAT-enhancer binding protein homologous protein. Meanwhile, the enhanced expression levels of these proteins were reversed by TUDCA, indicating that MA administration induced memory loss by evoking ER stress in the hippocampus. We also found that MA inhibited the induction of long-term potentiation (LTP) in the hippocampus. Nevertheless, LTP could be induced when mice were pre-treated with TUDCA. In conclusion, MA inhibited long-term memory acquisition and synaptic plasticity via ER stress. Frontiers Media S.A. 2021-01-14 /pmc/articles/PMC7840888/ /pubmed/33519373 http://dx.doi.org/10.3389/fnins.2020.630713 Text en Copyright © 2021 Chen, Wei, Xu, Yu, Yong, Su and Tao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Chen, Guang
Wei, Xiaoning
Xu, Xiang
Yu, Gang
Yong, Zheng
Su, Ruibin
Tao, Luyang
Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress
title Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress
title_full Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress
title_fullStr Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress
title_full_unstemmed Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress
title_short Methamphetamine Inhibits Long-Term Memory Acquisition and Synaptic Plasticity by Evoking Endoplasmic Reticulum Stress
title_sort methamphetamine inhibits long-term memory acquisition and synaptic plasticity by evoking endoplasmic reticulum stress
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840888/
https://www.ncbi.nlm.nih.gov/pubmed/33519373
http://dx.doi.org/10.3389/fnins.2020.630713
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