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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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5217670 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes.

Zhang Yue Y Xu Song S Liang Kang-Yan KY Li Kai K Zou Zhi-Peng ZP Yang Cui-Lan CL Tan Kang K Cao Xiong X Jiang Yu Y Gao Tian-Ming TM Bai Xiao-Chun XC

The Journal of biological chemistry 20161128 1

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. Interes ...[more]

PMID: 27895121

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Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes.

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Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes.

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