Osteopontin-integrin signaling positively regulates neuroplasticity through enhancing neural autophagy in the peri-infarct area after ischemic stroke

  • Am J Transl Res. 2022 Nov 15;14(11):7726-7743.
Haikang Liao  1  2  3 ,  Zhenyou Zou  1 ,  Weiqin Liu  4 ,  Xuefeng Guo  5 ,  Jinlu Xie  6 ,  Liangxian Li  1 ,  Xia Li  1 ,  Xinying Gan  1 ,  Xiansheng Huang  1 ,  Juxia Liu  1 ,  Wenyang Li  1 ,  Hongji Zeng  1 ,  Zheng Chen  1  6 ,  Qiuhua Jiang  4 ,  Hua Yao  1
Affiliations
  • 1. Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University Guilin, Guangxi, China.
  • 2. Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging Wenzhou Medical University, Oujiang Laboratory Wenzhou, Zhejiang, China.
  • 3. Institute of Neurology and Chemistry Wenzhou University Wenzhou, Zhejiang, China.
  • 4. The Ganzhou People's Hospital Ganzhou, Jiangxi, China.
  • 5. Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University Guilin, Guangxi, China.
  • 6. School of Medicine, Huzhou University, Huzhou Central Hospital Huzhou, Zhejiang, China.
PMID: 36505285
Abstract

Objective: To investigate the role of Osteopontin (OPN) in mediating macroautophagy, Autophagy, and neuroplasticity in the ipsilateral hemisphere after stroke.

Methods: Focal stroke was induced by photothrombosis in adult mice. Spatiotemporal expression of endogenous OPN and BECN1 was assessed by immunohistochemistry. Motor function was determined by the grid-walking and cylinder tasks. We also evaluated markers of neuroplasticity and Autophagy using biochemical and histology analyses.

Results: Herein, we showed that endogenous OPN and Beclin1 were increased in the peri-infarct area of stroked patients and mice. Intracerebral administration of OPN (0.1 mg/ml; 3 ml) significantly improved performance in motor behavioral tasks compared with non-OPN-treated stroke mice. Furthermore, the neural repair was induced in OPN-treated stroke mice. We found that OPN treatment resulted in a significantly higher density of a presynaptic marker (vesicular glutamate transporter 1, VgluT1) and synaptic plasticity marker (synaptophysin, SYN) within the peri-infarct region. OPN treatment in stroke mice not only increased protein levels of Integrin β1 but also promoted the expression of Beclin1 and LC3, two autophagy-related proteins in the peri-infarct area. Additionally, OPN-induced neuroplasticity and Autophagy were blocked by an Integrin antagonist.

Conclusion: Our findings indicate that OPN may enhance neuroplasticity via Autophagy, providing a new therapeutic strategy for ischemic stroke.

Keywords
Ischemic stroke; autophagy; motor functional recovery; neuroplasticity; osteopontin.
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