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  3. Neuregulin-1/PI3K signaling effects on oligodendrocyte proliferation, remyelination and behaviors deficit in a male mouse model of ischemic stroke

Neuregulin-1/PI3K signaling effects on oligodendrocyte proliferation, remyelination and behaviors deficit in a male mouse model of ischemic stroke

  • Exp Neurol. 2023 Jan 20;362:114323. doi: 10.1016/j.expneurol.2023.114323.
Mai Yin Cui 1,  Yan Qiong Fu 2,  Zhuo Li Li 2,  Yu Zheng 2,  Yi Yu 3,  Chan Zhang 4,  Yun Qi Zhang 5,  Bing Rui Gao 6,  Wu Yue Chen 7,  Yun-Lyul Lee 8,  Moo-Ho Won 9,  Min Liao 10,  Yong Jian 11,  Bai Hui Chen 12
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China; Department of Rehabilitation and Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310051, Zhejiang, PR China.
  • 2 Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China.
  • 3 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China.
  • 4 School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China.
  • 5 Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200023, PR China.
  • 6 Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
  • 7 The First School of Clinical Medicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China.
  • 8 Department of Physiology, College of Medicine, and Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon 24252, Gangwon, South Korea.
  • 9 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Gangwon, South Korea.
  • 10 Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China. Electronic address: [email protected].
  • 11 Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, Zhejiang, PR China. Electronic address: [email protected].
  • 12 Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China. Electronic address: [email protected].
PMID: 36690057 DOI: 10.1016/j.expneurol.2023.114323
Abstract

In this study, we investigated the effect of neuregulin-1 (NRG1) on demyelination and neurological function in an ischemic stroke model, and further explored its neuroprotective mechanisms. Adult male ICR mice underwent photothrombotic ischemia surgery and were injected with NRG1 beginning 30 min after ischemia. Cylinder and grid walking tests were performed to evaluate the forepaw function. In addition, the effect of NRG1 on neuronal damage/death (Cresyl violet, CV), neuronal nuclei (NeuN), nestin, doublecortin (DCX), myelin basic protein (MBP), non-phosphorylated neurofilaments (SMI-32), adenomatous polyposis coli (APC), erythroblastic leukemia viral oncogene homolog (ErbB) 2, 4 and serine-threonine protein kinase (Akt) in cortex were evaluated using immunohistochemistry, immunofluorescence and western blot. The cylinder and grid walking tests exposed that treatment of NRG1 observably regained the forepaw function. NRG1 treatment reduced cerebral infarction, restored forepaw function, promoted proliferation and differentiation of neuron and increased oligodendrogliogenesis. The neuroprotective effect of NRG1 is involved in its activation of PI3K/Akt signaling pathway via ErbB2, as shown by the suppression of the effect of NRG1 by the PI3K Inhibitor LY294002. Our results demonstrate that NRG1 is effective in ameliorating the both acute phase neuroprotection and long-term neurological functions via resumption of neuronal proliferation and differentiation and oligodendrogliogenesis in a male mouse model of ischemic stroke.

Keywords

ErbB2; Ischemic stroke; Myelin; Neuregulin-1; Oligodendrocyte; PI3K.

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