title: Immune-related GTPase M (IRGM1) regulates neuronal autophagy in a mouse model of stroke.
abstract: Autophagy is an important cellular recycling mechanism through self-digestion in responses to cellular stress such as starvation. Studies have shown that autophagy is involved in maintaining the homeostasis of the neural system during stroke. However, molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. Previously, we and others have shown that immune-related GTPase M (IRGM; termed IRGM1 in the mouse nomenclature) can regulate the survival of immune cells through autophagy in response to infections and autoimmune conditions. Here, using a permanent middle cerebral artery occlusion (pMCAO) mouse model, we found that IRGM1 was upregulated in the ischemic side of the brain, which was accompanied by a significant autophagic response. In contrast, neuronal autophagy was almost complete lost in Irgm1 knockout (KO) mice after pMCAO induction. In addition, the infarct volume in the Irgm1-KO pMCAO mice was significantly increased as compared to wild-type mice. Histological studies suggested that, at the early stage (within 24 h) of ischemia, the IRGM1-dependent autophagic response is associated with a protection of neurons from necrosis in the ischemic core but a promotion of neuronal apoptosis in the penumbra area. These data demonstrate a novel role of IRGM1 in regulating neuronal autophagy and survival during ischemic stroke.
authors.affiliation: Department of Immunology, Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: He
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.forename: Fucan
authors.initials: F
authors.lastname: Xia
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Jiang
authors.forename: Chunying
authors.initials: C
authors.lastname: Pei
authors.forename: Huan
authors.initials: H
authors.lastname: Ren
authors.forename: Huashun
authors.initials: H
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D009474:Neurons / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D020521:Stroke / Q000201:enzymology* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C096000:Ifi1 protein, mouse; D019204:GTP-Binding Proteins