Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission

Y. F. Guan; C. Y. Wu; Y. Y. Fang; Y. N. Zeng; Z. Y. Luo; S. J. Li; X. W. Li; X. H. Zhu; L. Mei; T. M. Gao

doi:10.1016/j.neuroscience.2015.08.047

Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission

Y. F. Guan, C. Y. Wu, Y. Y. Fang, Y. N. Zeng, Z. Y. Luo, S. J. Li, X. W. Li, X. H. Zhu, L. Mei, T. M. Gao

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4 inhibition. In addition, γ-Aminobutyric acid (GABA) receptor agonists had no synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD was partly blocked by GABA receptor antagonists. Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.

Original language	English (US)
Pages (from-to)	151-159
Number of pages	9
Journal	Neuroscience
Volume	307
DOIs	https://doi.org/10.1016/j.neuroscience.2015.08.047
State	Published - Oct 29 2015

Keywords

Apoptosis
ErbB4
GABA
NRG1
OGD
Stroke

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.neuroscience.2015.08.047

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@article{b09bb32f69ef4e63825e6fca4404340a,

title = "Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission",

abstract = "Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4 inhibition. In addition, γ-Aminobutyric acid (GABA) receptor agonists had no synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD was partly blocked by GABA receptor antagonists. Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.",

keywords = "Apoptosis, ErbB4, GABA, NRG1, OGD, Stroke",

author = "Guan, {Y. F.} and Wu, {C. Y.} and Fang, {Y. Y.} and Zeng, {Y. N.} and Luo, {Z. Y.} and Li, {S. J.} and Li, {X. W.} and Zhu, {X. H.} and L. Mei and Gao, {T. M.}",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (grants 81030022 , 81329003 and U1201225 ), Guangzhou Science and Technology Project (grant 201300000093 ) and Specialized Research Fund for the Doctoral Program of Higher Education of China (grant 20134433130002 ). Publisher Copyright: {\textcopyright} 2015 IBRO.",

year = "2015",

month = oct,

day = "29",

doi = "10.1016/j.neuroscience.2015.08.047",

language = "English (US)",

volume = "307",

pages = "151--159",

journal = "Neuroscience",

issn = "0306-4522",

publisher = "Elsevier Limited",

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TY - JOUR

T1 - Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission

AU - Guan, Y. F.

AU - Wu, C. Y.

AU - Fang, Y. Y.

AU - Zeng, Y. N.

AU - Luo, Z. Y.

AU - Li, S. J.

AU - Li, X. W.

AU - Zhu, X. H.

AU - Mei, L.

AU - Gao, T. M.

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (grants 81030022 , 81329003 and U1201225 ), Guangzhou Science and Technology Project (grant 201300000093 ) and Specialized Research Fund for the Doctoral Program of Higher Education of China (grant 20134433130002 ). Publisher Copyright: © 2015 IBRO.

PY - 2015/10/29

Y1 - 2015/10/29

N2 - Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4 inhibition. In addition, γ-Aminobutyric acid (GABA) receptor agonists had no synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD was partly blocked by GABA receptor antagonists. Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.

AB - Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. In this study, NRG1 rescued cortical neurons from oxygen-glucose deprivation (OGD) model, but the effect was blocked by neutralizing NRG1 and ErbB4 inhibition. In addition, γ-Aminobutyric acid (GABA) receptor agonists had no synergistic effect with NRG1, and the neuroprotective effect of NRG1 against OGD was partly blocked by GABA receptor antagonists. Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.

KW - Apoptosis

KW - ErbB4

KW - GABA

KW - NRG1

KW - OGD

KW - Stroke

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Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission

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