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

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.

SUBMITTER: Liao H 

PROVIDER: S-EPMC9730111 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature