Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal cortex during working memory performance of aged rats

Xinyu Xu; Xin Tian; Guolin Wang

doi:10.1016/j.biopha.2018.07.043

Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal cortex during working memory performance of aged rats

Biomed Pharmacother. 2018 Oct:106:1258-1266. doi: 10.1016/j.biopha.2018.07.043. Epub 2018 Jul 20.

Authors

Xinyu Xu¹, Xin Tian², Guolin Wang³

Affiliations

¹ Laboratory of Neurobiology in Medicine, School of Biomedical Engineering, Tianjin Medical University, Tianjin 300070, China.
² Laboratory of Neurobiology in Medicine, School of Biomedical Engineering, Tianjin Medical University, Tianjin 300070, China. Electronic address: [email protected].
³ Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Institute of Anesthesiology, Tianjin 300052, China. Electronic address: [email protected].

PMID: 30119195
DOI: 10.1016/j.biopha.2018.07.043

Abstract

Background: Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to evaluate the effects of sevoflurane on working memory of rats and to characterize functional connectivity between excitatory neurons in the prefrontal cortex (PFC) during working memory performance.

Methods: 18-month-old and 3-month-old male SD rats were implanted with a multielectrode array in the PFC. After recovery from the surgery, the aged and adult rats were divided into sevoflurane group and control group, respectively. Rats in sevoflurane group were exposed to 1 minimum alveolar concentration (MAC) or 1.5 MAC sevoflurane for two hours. At day1, 3, and 7 after exposure, the effects of sevoflurane anesthesia on working memory were investigated in the aged and adult rats by using delayed alternation in Y-maze. Spike trains of excitatory neurons in the PFC were recorded with the multielectrode array while rats were undergoing working memory performance. Functional connectivity between PFC excitatory neurons was described by Granger causal connectivity analysis.

Results: In adult rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1 after exposure (P < 0.01). However, in aged rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1, 3, and 7 after exposure (P < 0.01). 1 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons of aged rats at day1 after exposure (P < 0.01), but it had no effect in adult rats.

Conclusions: Sevoflurane-induced working memory impairment may depend on advanced age and anesthetic concentration. These findings also suggest, in rats, that sevoflurane-induced working memory impairment may be related to the decreased functional connectivity between PFC excitatory neurons.

Keywords: Excitatory neurons; Functional connectivity; Rats; Sevoflurane; Working memory.

MeSH terms

Action Potentials / drug effects
Age Factors
Anesthetics, Inhalation / toxicity*
Animals
Behavior, Animal / drug effects*
Dose-Response Relationship, Drug
Male
Maze Learning / drug effects
Memory Disorders / chemically induced*
Memory Disorders / pathology
Memory Disorders / physiopathology
Memory, Short-Term / drug effects*
Neurons / drug effects*
Neurons / pathology
Prefrontal Cortex / drug effects*
Prefrontal Cortex / pathology
Prefrontal Cortex / physiopathology
Rats, Sprague-Dawley
Sevoflurane / toxicity*
Time Factors

Substances

Anesthetics, Inhalation
Sevoflurane