ABSTRACT
Background
Sevoflurane treatment increases the incidence of postoperative cognitive dysfunction (POCD), and patients with POCD show a decline in cognitive abilities compared to preoperative levels.
Objectives
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.
Methods
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.
Results
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.
Conclusion
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.
HIGHLIGHTS
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.
SIGNIFICANCE STATEMENT
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.
Acknowledgments
The authors would like to acknowledge the technical support provided by the National Natural Science Foundation of China.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
Yuan Ge designed the experiment. Lei Ming analyzed the data. Dedong Xu supervised the study. Yuan Ge drafted the manuscript. All the authors have approved the submission.
Ethical approval
The experiments were performed at the Department of Anesthesiology, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan 250,013, China, and were approved by the Experimental Ethics Committee of the Central Hospital Affiliated to Shandong First Medical University. All methods were carried out in accordance with relevant guidelines and regulations. All methods are reported in accordance with ARRIVE guidelines (https://arriveguidelines.org).
Informed consent
This article does not contain any studies with human participants performed by any of the authors.
Consent to publish
All the authors have consent to publish.
Data availability statement
All processed data used in this study can be obtained from the corresponding author upon reasonable request.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/01616412.2024.2338031