Autophagy of Spinal Microglia Affects the Activation of Microglia through the PI3K/AKT/mTOR Signaling Pathway. (1st February 2022)

• Record Type: Journal Article
• Authors: Li, Jingjuan; Cheng, Xin; Fu, Dan; Liang, Yi; Chen, Cai; Deng, Wei; He, Liang
• Is Part Of: Neuroscience. Volume 482(2022)
• Page Start: 77
• Page End: 86
• Publication Date: 2022-02-01
• Subjects: 3-MA 3-Methyladenine -- IL-1β interleukin 1β -- IL-6 interleukin 6 -- ISCI ischemic spinal cord injury -- OGD oxygen and glucose deprivation -- PVDF polyvinylidene fluoride; ischemic spinal cord ischemia (ISCI) -- mild hypothermia -- microglia -- autophagy -- the PI3K/AKT/mTOR signaling -- rapamycin; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.12.005
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Mild hypothermia reduced the activation of microglia activation in ISCI rats. Mild hypothermia enhanced the autophagy in activated microglia. Rapamycin inhibited OGD induced microglia activation. Abstract: Delayed paralysis occurs within some patients suffered from ischemic spinal cord injury (ISCI) due to the aorta occlusion during the repair surgery of thoracic and thoracoabdominal aortic aneurysms. Although mild hypothermia has been reported to improve ISCI and prolong the tolerance of rats to ISCI without inducing immediate paralysis, the mechanism remains unclear. Herein, the study revealed that the mild hypothermia treatment indeed partially improved the ISCI in rats caused by cross-clamping at the descending aorta. ISCI induced the excessive activation of microglia and moderate autophagy in the spinal cord tissues of rats, while mild hypothermia significantly induced autophagy and reversed the excessive activation of microglia in the spinal cord tissues of rats. In OGD-stimulated mouse microglia BV-2 cells, the excessive activation of microglia and moderate autophagy were also observed; in the rapamycin-treated OGD model in BV-2 cells, autophagy was significantly enhanced whereas the excessive activation of microglia was reversed. In both in vivo ISCI model in rats and in vitro OGD model in BV-2 cells, the PI3K/AKT/mTOR pathway showed to be inhibited, whereas the PI3K/AKT/mTOR pathway was further inhibited by mild hypothermia in ISCI rats or rapamycin treatment in OGD-stimulated BV-2 cells. In conclusion, enhanced autophagy might be the mechanism of inhibited microglia activation by hypothermia treatment in ISCI rats and by rapamycin treatment in OGD-stimulated BV-2 cells. Autophagy could be enhanced through inhibiting the PI3K/AKT/mTOR pathway.