Gα13-Mediated Signaling Cascade Is Related to the Tau Pathology Caused by Anesthesia and Surgery in 5XFAD Transgenic Mice

Background: Our previous studies indicated that anesthesia and surgery could aggravate cognitive impairment of 5XFAD transgenic (Tg) mice, and this aggravation was associated with tau hyperphosphorylation. We previously identified that GNA13 (the gene encoding G alpha 13) was a hub gene with tau hyperphosphorylation. Objective: This study aims to further investigate the mechanism that whether the G alpha 13-mediated signaling pathway acts as an instigator to regulate cofilin activation and autophagy impairment in this process. Methods: 5XFAD Tg mice and their littermate (LM) mice were randomly allocated into four groups: LM Control group, LM Anesthesia/Surgery group, AD Control group, and AD Anesthesia/Surgery group. For mice in the Anesthesia/Surgery groups, abdominal surgery was performed under 1.4% isoflurane anesthesia followed by sustaining anesthetic inhalation for up to 2 h. Results: Compared with theADControl group, protein levels of G alpha 3, ROCK2, LPAR5, and p-tau/tau46 ratio were increased, while p-cofilin/cofilin protein expression ratio was decreased in the AD Anesthesia/Surgery group. However, the differences in these protein levels were not significant among LM groups. Conclusion: This study demonstrated that anesthesia and surgery might exacerbate p-tau accumulation in 5XFAD Tg mice but not in LM mice. And this might be closely related to cofilin activation via G alpha 13-mediated signaling cascade.