Sevoflurane-induced cognitive effect on α7-nicotine receptor and M₁ acetylcholine receptor expression in the hippocampus of aged rats

Sevoflurane treatment increases the incidence of postoperative cognitive dysfunction (POCD), and patients with POCD show a decline in cognitive abilities compared to preoperative levels. This study aimed to investigate whether the activation of α7 nicotinic acetylcholine receptor (α7nAChR) and the expression of M1 acetylcholine receptor (mAChR M1) in the hippocampus affects the cognitive function of aged rats. Forty-eight Sprague-Dawley (SD) rats of 1-week- and 12-months-old were divided into eight groups: four groups for α7nAChR and four groups for mAChR M1, respectively. All SD rats received 1.0–02% sevoflurane for α7nAChR and 1.0–02% sevoflurane for mAChR M1 for 2–6 h, respectively. The Y-maze test was used to assess the ability to learn and memory after receiving sevoflurane for 7 days at the same moment portion. RT-PCR was used to determine the expression of α7nAChR and mAChR M1 in the hippocampus of rats. The α7nAChR mitigated the formation of sevoflurane-induced memory impairment by modulating the translocation of NR2B from the intracellular reservoir to the cell surface reservoir within the hippocampus. Next, sevoflurane-induced decline of cognitive function and significantly decreased mAChR M1 expression at mRNA levels. α7nAChR regulates the trafficking of NR2B in the hippocampus of rats via the Src-family tyrosine kinase (SFK) pathway. This regulation is associated with cognitive deficits induced by sevoflurane in hippocampal development. Sevoflurane affects the cognitive function of rats by suppressing the mAChR M1 expression at mRNA levels in the hippocampus. α7nAChR attenuates sevoflurane-induced memory deficits by regulating NR2B. α7nAChR controls NR2B via the SFK in the hippocampus of rats that contribute to sevoflurane-induced cognitive deficits. Sevoflurane may affect cognitive function in rats by suppressing the mAChR M1 expression at the mRNA levels in the hippocampus. Dysregulation of the α7nAChR and mAChR M1 receptors may contribute to cognitive deficits and neurodegenerative disorders. α7nAChR attenuates sevoflurane-induced memory deficits by regulating NR2B. α7nAChR controls NR2B via the SFK in the hippocampus of rats that contribute to sevoflurane-induced cognitive deficits. Sevoflurane may affect cognitive function in rats by suppressing the mAChR M1 expression at the mRNA levels in the hippocampus. Dysregulation of the α7nAChR and mAChR M1 receptors may contribute to cognitive deficits and neurodegenerative disorders. Results provide key insights into the cognitive effects of sevoflurane, a commonly used anesthetic, on the expression of the α7nAChR and mAChR M1 in the hippocampus of aged rats. Activation of α7nAChR may attenuate sevoflurane-induced memory deficits by regulating the trafficking of NR2B in the hippocampus. Sevoflurane administration could temporarily impair cognitive function in rats by suppressing the expression of the mAChR M1 at the mRNA level in the hippocampus. These findings advance our understanding of the mechanisms underlying sevoflurane-induced POCD and provide implications for the prevention and treatment of the cognitive deficits associated with anesthesia in aging populations.七氟烷（sevoflurane）治疗会增加术后认知功能障碍（postoperative cognitive dysfunction, POCD）的发生率，且出现POCD的患者认知能力较术前水平出现下降。 本研究旨在探讨海马体内α7烟碱型乙酰胆碱受体（α7 nicotinic acetylcholine receptor, α7nAChR）的激活与M1型毒蕈碱型乙酰胆碱受体（M1 acetylcholine receptor, mAChR M1）的表达是否会影响老年大鼠的认知功能。 将48只1周龄及12月龄的斯普拉格-道利（SD）大鼠分为8组：分别用于α7nAChR与mAChR M1研究的组各4组。所有SD大鼠分别接受1.0%~0.2%七氟烷处理，时长2~6小时。于给药7天后的相同时段开展Y迷宫实验（Y-maze test），以评估大鼠的学习记忆能力。采用逆转录聚合酶链反应（RT-PCR）检测大鼠海马体内α7nAChR与mAChR M1的表达水平。 α7nAChR可通过调控NR2B从细胞内储备池向细胞表面储备池的跨膜转运，缓解七氟烷诱导的记忆损伤。进一步研究发现，七氟烷会导致大鼠认知功能下降，并显著降低mAChR M1的mRNA表达水平。 α7nAChR可通过Src家族酪氨酸激酶（Src-family tyrosine kinase, SFK）通路调控大鼠海马体内NR2B的转运，该调控过程与七氟烷诱导的海马发育相关认知缺陷有关。七氟烷可通过抑制大鼠海马体内mAChR M1的mRNA表达水平，影响其认知功能。 α7nAChR通过调控NR2B缓解七氟烷诱导的记忆缺陷。 α7nAChR可通过SFK通路调控大鼠海马体内的NR2B，进而参与七氟烷诱导的认知缺陷进程。 七氟烷可能通过抑制大鼠海马体内mAChR M1的mRNA表达水平，影响其认知功能。 α7nAChR与mAChR M1受体的表达失调，可能参与认知缺陷与神经退行性疾病的发生发展。 α7nAChR通过调控NR2B缓解七氟烷诱导的记忆缺陷。 α7nAChR可通过SFK通路调控大鼠海马体内的NR2B，进而参与七氟烷诱导的认知缺陷进程。 七氟烷可能通过抑制大鼠海马体内mAChR M1的mRNA表达水平，影响其认知功能。 α7nAChR与mAChR M1受体的表达失调，可能参与认知缺陷与神经退行性疾病的发生发展。 本研究结果为解析临床常用麻醉剂七氟烷对老年大鼠海马体内α7nAChR与mAChR M1表达的认知影响提供了关键见解。激活α7nAChR或可通过调控大鼠海马体内NR2B的转运，缓解七氟烷诱导的记忆缺陷。七氟烷给药可通过抑制海马体内mAChR M1的mRNA表达水平，暂时性损伤大鼠认知功能。上述发现加深了我们对七氟烷诱导POCD潜在机制的理解，也为老年群体麻醉相关认知缺陷的防治提供了新思路。