Mechanistic study of platelet-derived exosome-mediated miR-320a on attenuation of schizophrenia-like behavior in rat models via ITGβ modulation.

Abstract

BACKGROUND: MiRNA-320a is aberrantly expressed in individuals with schizophrenia, and integrin β1 (ITGβ1) has been identified as a direct target of miRNA-320a. ITGβ1 may play a role in neurotransmitter-related signaling pathways that contribute to the pathophysiology of schizophrenia. OBJECTIVE: This study aimed to investigate the potential of platelet-derived exosomes as a drug delivery vehicle for miR-320a to alleviate schizophrenia-like behavioral manifestations. METHODS: Platelet-derived exosomes were loaded with miR-320a via electroporation. Schizophrenia model rats were established using MK-801. The behavioral changes in the rats were assessed using the Morris water maze test and the open field test. Additionally, quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of miR-320a and ITGβ in the rat brain tissue. Furthermore, ultra-high-pressure liquid chromatography-tandem mass spectrometry (LC-MS) was used to analyze the levels of various neurotransmitters in the rat brain. RESULTS: Our findings indicated that treatment with platelet exosomes delivering miR-320 significantly improved the anxiety behavior and cognitive function of the rats with the schizophrenia model. The results showed that platelet exosomes loaded with miR-320a could significantly downregulate the expression of ITGβ, and LC-MS analysis indicated a decreasing trend in serotonin (5-HT). CONCLUSION: The findings of this study offer a novel perspective on the treatment of schizophrenia and suggest that P-exos-miR-320a may represent a promising therapeutic strategy, though further validation is needed.