HOMER1A restores sevoflurane-induced cognitive dysfunction by regulating microglia's activation through activating the AMPK/TXNIP axis

Abstract

More and more researchers have discovered that the employment of anesthetics can lead to cognitive dysfunction of brain. HOMER1A has been investigated to have neuroprotective effects. Sevoflurane (SEV) is the most common inhaled anesthetic utilized in surgery, but the role of HOMER1A in SEV-induced cognitive dysfunction is unclear. Thus, in this study, SEV was utilized in our study for investigating the role of HOMER1A. At first, the rat model was established through inhaling 2% SEV. Results from our study uncovered that the brain tissues of SEV-treated rats were severely damaged, and the levels of S-100β and neuron-specific enolase (NSE) were markedly elevated after SEV treatment. Further study showed that HOMER1A exhibited lower expression in the brain tissues of SEV-mediated rats. In addition, HOMER1A ameliorated nerve injury and cognitive deficit in SEV-treated rats. Moreover, HOMER1A improved inflammation in the brain tissues of SEV-induced rats. HOMER1A suppressed SEV-stimulated microglial activation through modulating M1/M2 polarization. Besides, HOMER1A activated Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) pathway to reduce thioredoxin interacting protein (TXNIP) expression. Finally, through rescue assays, inhibition of AMPK activation (Compound C (CC) treatment) attenuated the neuroprotective effects of HOMER1A in SEV-triggered rats. In summary, HOMER1A regulated microglia M1/M2 polarization to restore SEV-stimulated cognitive dysfunction through activating the AMPK/TXNIP axis.