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

doi:10.3389/fncel.2022.969261

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 journal › Article › peer-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 language	English
Article number	969261
Journal	Frontiers in Cellular Neuroscience
Volume	16
DOIs	https://doi.org/10.3389/fncel.2022.969261
State	Published - 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.

Funders	Funder number
National Institutes of Health (NIH)
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	RO1NS121193
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
American the American Heart Association	18CDA34060059
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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10.3389/fncel.2022.969261

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title = "LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting",

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.",

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author = "Meifan Chen and Laura Ingle and Plautz, \{Erik J.\} and Xiangmei Kong and Rui Tang and Neil Ghosh and Romprey, \{Megan K.\} and Fenske, \{William K.\} and Goldberg, \{Mark P.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Chen, Ingle, Plautz, Kong, Tang, Ghosh, Romprey, Fenske and Goldberg.",

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AU - Ingle, Laura

AU - Plautz, Erik J.

AU - Kong, Xiangmei

AU - Tang, Rui

AU - Ghosh, Neil

AU - Romprey, Megan K.

AU - Fenske, William K.

AU - Goldberg, Mark P.

PY - 2022/9/15

Y1 - 2022/9/15

N2 - 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.

AB - 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.

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KW - CNTF

KW - LZK/MAP3K13

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KW - axon sprouting

KW - reactive astrocytes

KW - stroke

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LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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