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Title: Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux

Abstract

Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux. - Highlights: • OGD/R impaires lysosomes and impedes the autophagic fluxmore » in hippocampal neurons. • Mild hypothermia rescues lysosomal function in neurons following OGD/R. • Mild hypothermia up-regulates the autophagic flux in neurons following OGD/R. • Mild hypothermia improves mitochondrial autophagy in neurons following OGD/R. • Chloroquine blocks the protective effects of mild hypothermia against OGD/R injury.« less

Authors:
;  [1];  [2]; ;  [1];  [1]
  1. Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120 (China)
  2. Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120 (China)
Publication Date:
OSTI Identifier:
22738153
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 358; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; HYPOTHERMIA; INJURIES; LYSOSOMES; MITOCHONDRIA; NERVE CELLS

Citation Formats

Zhou, Tianen, Liang, Lian, Liang, Yanran, Yu, Tao, Zeng, Chaotao, and Jiang, Longyuan. Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.06.010.
Zhou, Tianen, Liang, Lian, Liang, Yanran, Yu, Tao, Zeng, Chaotao, & Jiang, Longyuan. Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux. United States. doi:10.1016/J.YEXCR.2017.06.010.
Zhou, Tianen, Liang, Lian, Liang, Yanran, Yu, Tao, Zeng, Chaotao, and Jiang, Longyuan. Fri . "Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux". United States. doi:10.1016/J.YEXCR.2017.06.010.
@article{osti_22738153,
title = {Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux},
author = {Zhou, Tianen and Liang, Lian and Liang, Yanran and Yu, Tao and Zeng, Chaotao and Jiang, Longyuan},
abstractNote = {Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux. - Highlights: • OGD/R impaires lysosomes and impedes the autophagic flux in hippocampal neurons. • Mild hypothermia rescues lysosomal function in neurons following OGD/R. • Mild hypothermia up-regulates the autophagic flux in neurons following OGD/R. • Mild hypothermia improves mitochondrial autophagy in neurons following OGD/R. • Chloroquine blocks the protective effects of mild hypothermia against OGD/R injury.},
doi = {10.1016/J.YEXCR.2017.06.010},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 2,
volume = 358,
place = {United States},
year = {2017},
month = {9}
}