■我们先前的研究表明,麻醉/手术可以加重雌性5XFAD转基因(Tg)小鼠的认知障碍和tau病理。然而,尚不清楚5XFADTg小鼠发生术后认知功能障碍的易感性是否存在性别差异。
■在这项研究中,我们的目的是确定麻醉/手术是否对雌性和雄性5XFADTg小鼠有不同的影响,并探索支撑机制。
■小鼠在异氟烷麻醉下接受腹部手术。使用Morris水迷宫评估认知功能。海马p-tau水平(AT8),p-IRS1(Ser612),IRS1,p-GSK3β(Tyr216),和p-GSK3β(Ser9)在术后第1天通过蛋白质印迹测定进行评估。
■麻醉/手术夸大了女性的认知障碍和tau病理,但不是雄性5XFADTg小鼠。麻醉/手术导致女性海马蛋白水平升高的p-IRS1(Ser612)/IRS1比值和p-GSK3β(Tyr216)和海马蛋白水平降低的p-GSK3β(Ser9)。但不是雄性5XFADTg小鼠。
■这项研究表明,雌性5XFADTg小鼠更容易受到麻醉/手术引起的认知恶化和tau病理加重的影响,可能是由于女性特定的大脑胰岛素抵抗。
UNASSIGNED: Our previous studies indicated that anesthesia/surgery could aggravate cognitive impairment and tau pathology in female 5XFAD transgenic (Tg) mice. However, it is unknown whether there are sex differences in the susceptibility of developing postoperative cognitive dysfunction in 5XFAD Tg mice.
UNASSIGNED: In this study, we aim to determine whether anesthesia/surgery can have different effects on female and male 5XFAD Tg mice, and to explore the underpinning mechanisms.
UNASSIGNED: The mice received abdominal surgery under isoflurane anesthesia. Morris water maze was used to assess the cognitive function. Hippocampal levels of p-tau (AT8), p-IRS1 (Ser612), IRS1, p-GSK3β (Tyr216), and p-GSK3β (Ser9) at postoperative day 1 were evaluated by western blot assays.
UNASSIGNED: Anesthesia/surgery exaggerated cognitive impairment and tau pathology in female, but not male 5XFAD Tg mice. The anesthesia/surgery led to elevated hippocampus protein levels of p-IRS1 (Ser612)/IRS1 ratio and p-GSK3β (Tyr216) and reduced hippocampus protein levels of p-GSK3β (Ser9) in female, but not male 5XFAD Tg mice.
UNASSIGNED: This study demonstrated that female 5XFAD Tg mice were more susceptible to anesthesia/surgery-induced cognitive deterioration and tau pathology aggravation, potentially due to female-specific brain insulin resistance.