Effects of isoflurane on learning and memory and the expression of GRP78, ATF4 and CHOP in frontal lobe neurons of aged rats

Abstract

Objective To observe the changes of learning and memory ability and the expression of GRP8, ATF4 and CHOP in the frontal lobe neurons of rats after isoflurane anesthesia. Methods Male SD aged rats were randomly divided into 4 groups with 15 in each group. Rats in ISO group received 1.5% isoflurane 2 h, SAL group received intraperitoneal injection Salubrinal(1 mg/kg), ISO+ SAL group received 1.5% 2 h after intraperitoneal injection Salubrinal(1 mg/kg), C group only inhaled 30% air and oxygen mixture. Morris water maze (MWM) test was performed 24 hours after isoflurane anesthesia, and then the left frontal lobe of rats was collected, gene transcription and protein expression changes of 78-kDa glucose-regulated protein(GRP78), activating transcription factor 4(ATF4), C/EBP homologous protein(CHOP) were evaluated by real-time fluorescence quantitative PCR and immunofluorescence. Results Compared with the C group, the latent time of ISO group was significantly prolonged(ISO group(19.10±2.98)s vs C group (10.54±2.05)s, P<0.05) ; the number of times passing through the target platform of ISO group was decreased significantly(ISO group (6.78±1.47) vs Cgroup (9.03±1.69), P<0.05); protein expression level of GRP78 was significantly increased in group ISO (ISO group (965.8±86.5) vs C group(247.5±46.3), P<0.05); protein expression level of ATF4 was significantly increased in group ISO(ISO group (470±69.4) vs C group (275.4±56.3), P<0.05) protein expression level of CHOP was significantly increased in group ISO(ISO group (618.7±83.3) vs C group(174.5±71.2), P<0.05). The transcription trends of GRP78, ATF4, CHOP were consistent with their protein expression. Conclusion The decrease of short-term memory ability after isoflurane anesthesia may be related to the activation of endoplasmic reticulum stress pathway in frontal lobe neurons. Key words: Isofluane; Frontal lobe; Endoplasmic reticulum stress; GRP78; ATF4; CHOP