title: Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes.
abstract: Astrocytes respond to CNS insults through reactive astrogliosis, but the underlying mechanisms are unclear. In this study, we show that inactivation of mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller soma and fewer dendrites, resulting in microcephaly and aberrant behavior in adult mice. Interestingly, extensive astrogliosis without significant astrocyte proliferation and glial scar formation was observed in these mice. The inhibition of neuronal mTORC1 may activate astrogliosis by reducing neuron-derived fibroblast growth factor 2 (FGF-2), which might trigger FGF receptor signaling in astrocytes to maintain their nonreactive state, and FGF-2 injection successfully prevented astrogliosis in Raptor knock-out mice. This study demonstrates that neuronal mTORC1 inhibits reactive astrogliosis and plays an important role in CNS pathologies.
authors.affiliation: From the Academy of Orthopedics, Guangdong Province, the Third Affiliated Hospital, Southern Medical University, Guangzhou 510515, China.|the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Academy of Orthopedics, Guangdong Province, the Third Affiliated Hospital, Southern Medical University, Guangzhou 510515, China.|the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xu
authors.affiliation: the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kang-Yan
authors.initials: KY
authors.lastname: Liang
authors.affiliation: the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Zou
authors.affiliation: the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Cui-Lan
authors.initials: CL
authors.lastname: Yang
authors.affiliation: the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Tan
authors.affiliation: the Department of Neurobiology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China, and.
authors.forename: Xiong
authors.initials: X
authors.lastname: Cao
authors.affiliation: the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: the Department of Neurobiology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China, and.
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
authors.affiliation: From the Academy of Orthopedics, Guangdong Province, the Third Affiliated Hospital, Southern Medical University, Guangzhou 510515, China, baixc15@smu.edu.cn xiaochunbai@aliyun.com.|the Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Bai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001522:Behavior, Animal; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Raptor; astrocyte; fibroblast growth factor (FGF); fibroblast growth factor 2; mTOR complex (mTORC); mammalian target of rapamycin (mTOR); neuron; reactive astrogliosis