LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting

Meifan Chen, Laura Ingle, Erik J. Plautz, Xiangmei Kong, Rui Tang, Neil Ghosh, Megan K. Romprey, William K. Fenske, Mark P. Goldberg

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Injury to the adult mammalian central nervous system induces compensatory plasticity of spared axons—referred to as collateral axon sprouting—that can facilitate neural recovery. The contribution of reactive astrocytes to axon sprouting remains elusive. Here, we sought to investigate the role of axon degeneration-reactive astrocytes in the regulation of collateral axon sprouting that occurs in the mouse spinal cord after unilateral photothrombotic stroke of the primary motor cortex. We identified astrocytic leucine zipper-bearing kinase (LZK) as a positive regulator of astrocyte reactivity to corticospinal axon degeneration. Remarkably, genetic stimulation of astrocyte reactivity, via LZK overexpression in adult astrocytes, enhanced corticospinal axon sprouting. LZK promoted the production of astrocyte-derived ciliary neurotrophic factor (CNTF) that likely enhanced axon growth in mice with astrocytic LZK overexpression after injury. Our finding that LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting highlights the potential of engineering astrocytes to support injury-induced axon plasticity for neural repair.

Original languageEnglish
Article number969261
JournalFrontiers in Cellular Neuroscience
Volume16
DOIs
StatePublished - Sep 15 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Chen, Ingle, Plautz, Kong, Tang, Ghosh, Romprey, Fenske and Goldberg.

Funding

This work was supported by grants from American Heart Association (18CDA34060059) and NIH/NINDS (RO1NS121193) to MC, Kentucky Spinal Cord & Head Injury Research Trust training fund to Chen Lab, and the Haggerty Center for Brain Injury and Repair to MG.

FundersFunder number
National Institutes of Health (NIH)
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke CouncilRO1NS121193
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
American the American Heart Association18CDA34060059
American the American Heart Association

    Keywords

    • CNS injury
    • CNTF
    • LZK/MAP3K13
    • astrogliosis
    • axon plasticity
    • axon sprouting
    • reactive astrocytes
    • stroke

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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