Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor

Melissa M Gresle; Helmut Butzkueven; Victoria M Perreau; Anna Jonas; Junhua Xiao; Stefan Thiem; Fiona E Holmes; William Doherty; Pik-Ying Soo; Michele D Binder; Rainer Akkermann; Vilija G Jokubaitis; Holly S Cate; Mark P Marriott; Andrew L Gundlach; David Wynick; Trevor J Kilpatrick

doi:10.1002/glia.22798

Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor

Melissa M Gresle, Helmut Butzkueven, Victoria M Perreau, Anna Jonas, Junhua Xiao, Stefan Thiem, Fiona E Holmes, William Doherty, Pik-Ying Soo, Michele D Binder, Rainer Akkermann, Vilija G Jokubaitis, Holly S Cate, Mark P Marriott, Andrew L Gundlach, David Wynick, Trevor J Kilpatrick

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

In order to further investigate the molecular mechanisms that regulate oligodendrocyte (OC) survival, we utilized microarrays to characterize changes in OC gene expression after exposure to the cytokines neurotrophin3, insulin, or leukemia inhibitory factor (LIF) in vitro. We identified and validated the induction and secretion of the neuropeptide galanin in OCs, specifically in response to LIF. We next established that galanin is an OC survival factor and showed that autocrine or paracrine galanin secretion mediates LIF-induced OC survival in vitro. We also revealed that galanin is up-regulated in OCs in the cuprizone model of central demyelination, and that oligodendroglial galanin expression is significantly regulated by endogenous LIF in this context. We also showed that knock-out of galanin reduces OC survival and exacerbates callosal demyelination in the cuprizone model. These findings suggest a potential role for the use of galanin agonists in the treatment of human demyelinating diseases.

Original language	English
Pages (from-to)	1005-1020
Number of pages	16
Journal	Glia
Volume	63
Issue number	6
Early online date	29 Jan 2015
DOIs	https://doi.org/10.1002/glia.22798
Publication status	Published - Jun 2015

Keywords

leukemia inhibitory factor
galanin
oligodendrocytes

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10.1002/glia.22798

2016 Wynick 59208318
This is the peer reviewed version of the following article: Gresle, M. M., Butzkueven, H., Perreau, V. M., Jonas, A., Xiao, J., Thiem, S., Holmes, F. E., Doherty, W., Soo, P.-Y., Binder, M. D., Akkermann, R., Jokubaitis, V. G., Cate, H. S., Marriott, M. P., Gundlach, A. L., Wynick, D. and Kilpatrick, T. J. (2015), Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor. Glia, 63: 1005–1020, which has been published in final form at doi: 10.1002/glia.22798. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript, 1.21 MB

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THE ROLE OF GALANIN IN THE ADAPTIVE RESPONSE OF THE PERIPHERAL NERVOUS SYSTEMT O INJURY
Wynick, D.
1/08/03 → 1/08/08
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Professor David Wynick
- david.wynickbristol.acuk
- Bristol Medical School (THS) - Professor of Molecular Medicine
- Elizabeth Blackwell Institute for Health Research
- Bristol Neuroscience
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Gresle, M. M., Butzkueven, H., Perreau, V. M., Jonas, A., Xiao, J., Thiem, S., Holmes, F. E., Doherty, W., Soo, P-Y., Binder, M. D., Akkermann, R., Jokubaitis, V. G., Cate, H. S., Marriott, M. P., Gundlach, A. L., Wynick, D., & Kilpatrick, T. J. (2015). Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor. Glia, 63(6), 1005-1020. https://doi.org/10.1002/glia.22798

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title = "Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor",

abstract = "In order to further investigate the molecular mechanisms that regulate oligodendrocyte (OC) survival, we utilized microarrays to characterize changes in OC gene expression after exposure to the cytokines neurotrophin3, insulin, or leukemia inhibitory factor (LIF) in vitro. We identified and validated the induction and secretion of the neuropeptide galanin in OCs, specifically in response to LIF. We next established that galanin is an OC survival factor and showed that autocrine or paracrine galanin secretion mediates LIF-induced OC survival in vitro. We also revealed that galanin is up-regulated in OCs in the cuprizone model of central demyelination, and that oligodendroglial galanin expression is significantly regulated by endogenous LIF in this context. We also showed that knock-out of galanin reduces OC survival and exacerbates callosal demyelination in the cuprizone model. These findings suggest a potential role for the use of galanin agonists in the treatment of human demyelinating diseases.",

keywords = " leukemia inhibitory factor, galanin, oligodendrocytes",

author = "Gresle, {Melissa M} and Helmut Butzkueven and Perreau, {Victoria M} and Anna Jonas and Junhua Xiao and Stefan Thiem and Holmes, {Fiona E} and William Doherty and Pik-Ying Soo and Binder, {Michele D} and Rainer Akkermann and Jokubaitis, {Vilija G} and Cate, {Holly S} and Marriott, {Mark P} and Gundlach, {Andrew L} and David Wynick and Kilpatrick, {Trevor J}",

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year = "2015",

month = jun,

doi = "10.1002/glia.22798",

language = "English",

volume = "63",

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Gresle, MM, Butzkueven, H, Perreau, VM, Jonas, A, Xiao, J, Thiem, S, Holmes, FE, Doherty, W, Soo, P-Y, Binder, MD, Akkermann, R, Jokubaitis, VG, Cate, HS, Marriott, MP, Gundlach, AL, Wynick, D & Kilpatrick, TJ 2015, 'Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor', Glia, vol. 63, no. 6, pp. 1005-1020. https://doi.org/10.1002/glia.22798

TY - JOUR

T1 - Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor

AU - Gresle, Melissa M

AU - Butzkueven, Helmut

AU - Perreau, Victoria M

AU - Jonas, Anna

AU - Xiao, Junhua

AU - Thiem, Stefan

AU - Holmes, Fiona E

AU - Doherty, William

AU - Soo, Pik-Ying

AU - Binder, Michele D

AU - Akkermann, Rainer

AU - Jokubaitis, Vilija G

AU - Cate, Holly S

AU - Marriott, Mark P

AU - Gundlach, Andrew L

AU - Wynick, David

AU - Kilpatrick, Trevor J

PY - 2015/6

Y1 - 2015/6

N2 - In order to further investigate the molecular mechanisms that regulate oligodendrocyte (OC) survival, we utilized microarrays to characterize changes in OC gene expression after exposure to the cytokines neurotrophin3, insulin, or leukemia inhibitory factor (LIF) in vitro. We identified and validated the induction and secretion of the neuropeptide galanin in OCs, specifically in response to LIF. We next established that galanin is an OC survival factor and showed that autocrine or paracrine galanin secretion mediates LIF-induced OC survival in vitro. We also revealed that galanin is up-regulated in OCs in the cuprizone model of central demyelination, and that oligodendroglial galanin expression is significantly regulated by endogenous LIF in this context. We also showed that knock-out of galanin reduces OC survival and exacerbates callosal demyelination in the cuprizone model. These findings suggest a potential role for the use of galanin agonists in the treatment of human demyelinating diseases.

AB - In order to further investigate the molecular mechanisms that regulate oligodendrocyte (OC) survival, we utilized microarrays to characterize changes in OC gene expression after exposure to the cytokines neurotrophin3, insulin, or leukemia inhibitory factor (LIF) in vitro. We identified and validated the induction and secretion of the neuropeptide galanin in OCs, specifically in response to LIF. We next established that galanin is an OC survival factor and showed that autocrine or paracrine galanin secretion mediates LIF-induced OC survival in vitro. We also revealed that galanin is up-regulated in OCs in the cuprizone model of central demyelination, and that oligodendroglial galanin expression is significantly regulated by endogenous LIF in this context. We also showed that knock-out of galanin reduces OC survival and exacerbates callosal demyelination in the cuprizone model. These findings suggest a potential role for the use of galanin agonists in the treatment of human demyelinating diseases.

KW - leukemia inhibitory factor

KW - galanin

KW - oligodendrocytes

U2 - 10.1002/glia.22798

DO - 10.1002/glia.22798

M3 - Article (Academic Journal)

C2 - 25639936

VL - 63

SP - 1005

EP - 1020

JO - Glia

JF - Glia

SN - 0894-1491

IS - 6

ER -

Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor

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THE ROLE OF GALANIN IN THE ADAPTIVE RESPONSE OF THE PERIPHERAL NERVOUS SYSTEMT O INJURY

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