Abstract：
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 Gα13) was a hub gene with tau hyperphosphorylation.
This study aims to further investigate the mechanism that whether the Gα13-mediated signaling pathway acts as an instigator to regulate cofilin activation and autophagy impairment in this process.
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.
Compared with the AD Control group, protein levels of Gα13, 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.
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 Gα13-mediated signaling cascade.
This study aims to further investigate the mechanism that whether the Gα13-mediated signaling pathway acts as an instigator to regulate cofilin activation and autophagy impairment in this process.
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.
Compared with the AD Control group, protein levels of Gα13, 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.
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 Gα13-mediated signaling cascade.
摘要：
背景：我们以前的研究表明，麻醉和手术可以加重5XFAD转基因（Tg）小鼠的认知障碍，这种恶化与tau蛋白过度磷酸化有关。我们先前鉴定GNA13(编码Gα13的基因)是具有tau过度磷酸化的hub基因。
目的：本研究旨在进一步探讨Gα13介导的信号通路是否在该过程中作为促进因子调控cofilin激活和自噬损伤的机制。
方法：将5XFADTg小鼠及其同窝（LM）小鼠随机分为四组：LM对照组，LM麻醉/手术组，AD控制组,和AD麻醉/手术组。对于麻醉/手术组的小鼠，腹部手术在1.4%异氟烷麻醉下进行，然后持续吸入麻醉长达2小时。
结果：与AD对照组相比，Gα13，ROCK2，LPAR5和p-tau/tau46比值的蛋白质水平增加，而在AD麻醉/手术组中，p-cofilin/cofilin蛋白表达比率降低。然而,LM组之间这些蛋白质水平的差异不显著.
结论：这项研究表明，麻醉和手术可能会加剧5XFADTg小鼠的p-tau积累，但不会加剧LM小鼠的p-tau积累。这可能与通过Gα13介导的信号级联激活cofilin密切相关。
目的：本研究旨在进一步探讨Gα13介导的信号通路是否在该过程中作为促进因子调控cofilin激活和自噬损伤的机制。
方法：将5XFADTg小鼠及其同窝（LM）小鼠随机分为四组：LM对照组，LM麻醉/手术组，AD控制组,和AD麻醉/手术组。对于麻醉/手术组的小鼠，腹部手术在1.4%异氟烷麻醉下进行，然后持续吸入麻醉长达2小时。
结果：与AD对照组相比，Gα13，ROCK2，LPAR5和p-tau/tau46比值的蛋白质水平增加，而在AD麻醉/手术组中，p-cofilin/cofilin蛋白表达比率降低。然而,LM组之间这些蛋白质水平的差异不显著.
结论：这项研究表明，麻醉和手术可能会加剧5XFADTg小鼠的p-tau积累，但不会加剧LM小鼠的p-tau积累。这可能与通过Gα13介导的信号级联激活cofilin密切相关。
