Effect of ketamine anesthesia on proteome in hippocampus of aged rats

Abstract

Objective To evaluate the effects of ketamine anesthesia on proteome in hippocampus in aged rats. Methods Thirty healthy male Wistar rats, aged 20 months, weighing 560-610 g, were divided into 2 groups (n=15 each) using a random number table method: control group (group C) and ketamine group (group K). In group K, ketamine 80 mg/kg was intraperitoneally injected, additional 1/2 initial dose was given when the righting reflex was recovered, and anesthesia was maintained for 3 h. Morris water maze test was performed starting from 1st day after the end of anesthesia.Five rats were selected at days 1 and 7 after the end of anesthesia and sacrificed, and hippocampal tissues were obtained to extract proteins.Proteins extracted from rat hippocampi were identified by 2-dimensional electrophoresis (2-DE). The differentially expressed proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and biological information system. Results Compared with group C, the escape latency and total swimming distance to find the submerged platform in Morris water maze at the 1st day after anesthesia were significantly prolonged in group K (P<0.05 or 0.01). The MALDI-TOF-MS analysis showed that there were 21 differentially expressed proteins at 1st day after ketamine anesthesia, of which 6 proteins (involving maintenance of intracellular protein homeostasis, energy metabolism, etc.) presented with up-regulated expression and 15 proteins (involving synaptic vesicle transport efficiency, synaptic structural and functional plasticity, maintenance of intracellular protein homeostasis, NMDA-mediated Ca2+ signal transport, energy metabolism, etc.) presented with down-regulated expression.There were 8 differentially expressed proteins at 7th day, including 3 proteins with up-regulated expression and 5 proteins with down-regulated expression (P<0.05). Conclusion Ketamine anesthesia can induce 21 differentially expressed proteins in hippocampi of aged rats, involving synaptic vesicle transport efficiency, synaptic structural and functional plasticity, intracellular protein homeostasis, NMDA-mediated Ca2+ signal transport, energy metabolism, and etc.which may be involved in the mechanism of ketamine-induced temporary cognitive dysfunction. Key words: Ketamine; Cognitive function; Hippocampus; Proteome; Aged