Role of the hippocampal 5-HT1A receptor-mediated cAMP/PKA signalling pathway in sevoflurane-induced cognitivedysfunction in aged rats.J Int Med Res. 2018 Mar; 46(3):1073-1085.JI
Objective This study aimed to evaluate the role of the hippocampal 5-hydroxytryptamine-1A (5-HT1A)-mediated cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signalling pathway in sevoflurane-induced cognitive dysfunction in aged rats. Methods Sixty 18-month-old Sprague-Dawley rats were divided into the control (n = 30) and experimental (Sev, n = 30) groups. The experimental group inhaled 50% air/oxygen mixture (2 L/min) and 2% sevoflurane for 4 hours. The control group inhaled 50% air/oxygen mixture (2 L/min) for 4 hours. The Morris water maze test was performed The mRNA expression of 5-HT1A receptor, and cAMP PKA, cAMP response element-binding protein (CREB), and phosphorylated CREB (p-CREB) protein expression were determined. Results The escape latency and swimming distance were greater, and the number of crossings of the platform location and time spent in the platform quadrant were less in the Sev group compared with the control group. cAMP, PKA, CREB, and p-CREB protein expression was downregulated in the Sev group 1 day after anaesthesia compared with the control group. Hippocampal 5-HT1A receptor mRNA expression was higher 7 days after anaesthesia compared with the control group. Conclusion Sevoflurane-induced cognitive dysfunction in aged rats may be related to inhibited expression of the hippocampal 5-HT1A receptor-mediated cAMP/PKA signalling pathway.