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

Neuroscience. 2015 Oct 29:307:151-9. doi: 10.1016/j.neuroscience.2015.08.047. Epub 2015 Aug 28.

Authors

Y-F Guan¹, C-Y Wu², Y-Y Fang¹, Y-N Zeng¹, Z-Y Luo¹, S-J Li¹, X-W Li¹, X-H Zhu¹, L Mei³, T-M Gao⁴

Affiliations

¹ State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
² State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Bayi Brain Hospital, The Military General Hospital of Beijing PLA, Beijing 100700, China.
³ Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
⁴ State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: tgao@smu.edu.cn.

PMID: 26318331
DOI: 10.1016/j.neuroscience.2015.08.047

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: ErbB4; GABA; NRG1; OGD; apoptosis; stroke.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis / physiology
Brain Injuries / etiology
Brain Injuries / metabolism*
Brain Injuries / prevention & control*
Cell Hypoxia / drug effects
Cells, Cultured
Disease Models, Animal
GABA Agonists / pharmacology
Infarction, Middle Cerebral Artery / complications
Infarction, Middle Cerebral Artery / genetics
Male
Mice
Mice, Transgenic
Neuregulin-1 / pharmacology
Neuregulin-1 / therapeutic use*
Neurons / drug effects
Neuroprotective Agents / pharmacology
Neuroprotective Agents / therapeutic use*
Parvalbumins / metabolism
Rats
Receptor, ErbB-4 / genetics
Receptor, ErbB-4 / metabolism*
Synaptic Transmission / drug effects*
Synaptic Transmission / genetics
gamma-Aminobutyric Acid / metabolism*

Substances

GABA Agonists
Neuregulin-1
Neuroprotective Agents
Parvalbumins
gamma-Aminobutyric Acid
Erbb4 protein, mouse
Receptor, ErbB-4