Melatonin attenuates traumatic brain injury-induced inflammation: a possible role for mitophagy.
Melatonin functions as a crucial mediator of sterile neuroinflammation; however, the underlying mechanisms remain poorly understood. Dysfunctional mitochondria, a main source of reactive oxygen species, are impacted in inflammation activation. This study aimed to examine the effect of melatonin on inflammation via elimination of damaged mitochondria after controlled cortical impact, an in vivo model of traumatic brain injury (TBI). Here, we demonstrated that inhibition of mitophagy, the selective degradation of damaged mitochondria by autophagy, markedly enhanced inflammation induced by TBI. Melatonin treatment activated mitophagy through the mTOR pathway, then to attenuate TBI-induced inflammation. Furthermore, treatment with melatonin significantly ameliorated neuronal death and behavioral deficits after TBI, while 3-methyladenine reversed this effect by inhibiting mitophagy. Taken together, these results highlight a role for melatonin in protecting against TBI-triggered immunopathology, which is accomplished by negatively regulating inflammation activation and IL-1β secretion via the autophagy of damaged mitochondria.
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Chao
C
Lin
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Honglu
H
Chao
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Zheng
Z
Li
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Xiupeng
X
Xu
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yinlong
Y
Liu
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Lijun
L
Hou
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Ning
N
Liu
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jing
J
Ji
D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D063306:Mitophagy / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
C000594089:IL1B protein, rat; D053583:Interleukin-1beta; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D008550:Melatonin
inflammation; melatonin; mitophagy; traumatic brain injury