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.
authors: 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.
authors: Y-F
authors: YF
authors: Guan
authors: 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.
authors: C-Y
authors: CY
authors: Wu
authors: 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.
authors: Y-Y
authors: YY
authors: Fang
authors: 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.
authors: Y-N
authors: YN
authors: Zeng
authors: 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.
authors: Z-Y
authors: ZY
authors: Luo
authors: 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.
authors: S-J
authors: SJ
authors: Li
authors: 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.
authors: X-W
authors: XW
authors: Li
authors: 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.
authors: X-H
authors: XH
authors: Zhu
authors: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors: L
authors: L
authors: Mei
authors: 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.
authors: T-M
authors: TM
authors: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; D020890:Neuregulin-1; D018696:Neuroprotective Agents; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4
keywords: ErbB4; GABA; NRG1; OGD; apoptosis; stroke