Open AccessLiraglutide activates autophagyviaGLP-1R to improve functional recovery after spinal cord injury
Author(s) -
Jian Chen,
Zhouguang Wang,
Yuqin Mao,
Zengming Zheng,
Yu Chen,
Sinan Khor,
Kesi Shi,
Zili He,
Jiawei Li,
Fanghua Gong,
Yanlong Liu,
Aiping Hu,
Jian Xiao,
Xiangyang Wang
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.20791
Subject(s) - liraglutide , medicine , spinal cord injury , autophagy , spinal cord , diabetes mellitus , apoptosis , endocrinology , biology , type 2 diabetes , biochemistry , psychiatry
Therapeutics used to treat central nervous system (CNS) injury are designed to promote axonal regeneration and inhibit cell death. Previous studies have shown that liraglutide exerts potent neuroprotective effects after brain injury. However, little is known if liraglutide treatment has neuroprotective effects after spinal cord injury (SCI). This study explores the neuroprotective effects of liraglutide and associated underlying mechanisms. Our results showed that liraglutide could improve recovery after injury by decreasing apoptosis as well as increasing microtubulin acetylation, and autophagy. Autophagy inhibition with 3-methyladenine (3-MA) partially reversed the preservation of spinal cord tissue and decreased microtubule acetylation and polymerization. Additionally, siRNA knockdown of GLP-1R suppressed autophagy and reversed mTOR inhibition induced by liraglutide in vitro , indicating that GLP-1R regulates autophagic flux. GLP-1R knockdown ameliorated the mTOR inhibition and autophagy induction seen with liraglutide treatment in PC12 cells under H 2 O 2 stimulation. Taken together, our study demonstrated that liraglutide could reduce apoptosis, improve functional recovery, and increase microtubule acetylation via autophagy stimulation after SCI. GLP-1R was associated with both the induction of autophagy and suppression of apoptosis in neuronal cultures.