Sperm associated antigen 6 (Spag6) is the PF16 homolog of Chlamydomonas and participates in the regulation of cilia movement. Studies have shown that Spag6 is expressed in the brain, and its loss will lead to cerebral edema caused by a defect in motor cilium function in ependymal cells. However, it has not been reported whether the limited or extensive cerebral edema resulting from ischemic strokes is related to the expression regulation of Spag6. Therefore, this study aimed to investigate the effect and related mechanism of Spag6 in alleviating Cerebral Ischemic stroke-reperfusion (CIS/R) damage. Our experimental results showed that Spag6 overexpression alleviated CIS/R-mediated motor cilia structural disorder, improved cerebral edema, inhibited nerve injuries in rats with cerebral ischemia, and alleviated synaptic and dendritic spinal injuries by regulating the expressions of synaptic-related proteins such as CaMKII, PSD95, and CREB. Based on significant changes in PI3K/AKT-mTOR signaling pathway activity after CIS/R determination, we determined that Spag6 regulates the abnormal expression of CIS/R-induced inflammatory factors NF-κB, NLRP3, IL-10, and the autophagy-related proteins Beclin-1, LC3, and P62 by activating the PI3K/AKT-mTOR signaling pathway. This inhibits inflammation and autophagy in the brain tissue. In summary, this study revealed that Spag6 alleviates brain edema damage after CIS/R by maintaining the structural function of the motor cilium, regulating the PI3K/AKT-mTOR signaling pathway, and inhibiting inflammation and autophagy reaction.
Keywords: PI3K/AKT-mTOR signaling pathway; Spag6; autophagy; cerebral Ischemic stroke-reperfusion; inflammatory.
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