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

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.

GRAPHICAL ABSTRACT

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.

KEYWORDS:

• Sevoflurane
• cognitive effect
• α7nAChR
• mAchR M₁
• hippocampus

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

Additional information

Funding

This study was supported by the Jinan Municipal Health Commission Science and Technology Plan [Grant Fund Number: 2022-2-22].