title: Extra-cellular signal-regulated kinase (ERK) is inactivated associating hippocampal ARC protein up-regulation in sevoflurane induced bidirectional regulation of memory.
abstract: Low dose sevoflurane is demonstrated to have neuronal excitatory effects in the central nervous system. Activity-regulated cytoskeleton protein (Arc) can be rapidly expressed in the hippocampus for the modulation of synaptic plasticity. The extracellular signal-regulated kinase (ERK) pathway is also involved in learning and memory by mediating signals and modifications. This study aims at exploring the mechanism of sevoflurane on memory by connecting the ERK pathway, Arc and inhibitory avoidance (IA) behavioral training. SD rats were randomly assigned to three groups (sham, 0.11 and 0.3 % SEV). Anesthesia was given by target dose of sevoflurane for 45 min and IA (0.4 mA, 2 s) was conducted on every subject immediately after inhalation. The memory retention latency was observed 24 h after. Another serial of rats were sacrificed for Western-blot and polymerase chain reaction (PCR) examination of hippocampal tissue after first IA. 24 h IA performance was compared among groups. The 0.11 % SEV group displayed an elevation of memory retention, while the 0.3 % SEV group had decreased memory retention, both showed statistical differences from the sham (air) group. PCR analysis of Arc mRNA levels showed that subanesthetic doses of sevoflurane did not change Arc transcription levels between groups. However, 0.11 % sevoflurane significantly increased Arc protein in the hippocampus, while 0.3 % sevoflurane reversed this (*P < 0.05, compared with the sham group). There was no difference in total ERK between groups. Expression of phosphorylated ERK was significantly increased upon exposure to sevoflurane in a does dependent manner. ERK was down-regulated with hippocampal ARC expression in sevoflurane induced bidirectional regulation of memory, potentially at a translational level of modification.
authors.affiliation: Department of Anesthesiology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Qianlin
authors.initials: Q
authors.lastname: Zhu
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Xue
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Buwei
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000077149:Sevoflurane; D015854:Up-Regulation
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D008738:Methyl Ethers; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D000077149:Sevoflurane; D048049:Extracellular Signal-Regulated MAP Kinases