ABSTRACT
Objective To investigate the synergetic effect of combined astaxanthin ( AST) and lith-ium chloride ( LiCl) treatment on cognitive dysfunction of chronic omethoate poisoned mice. Methods 8 mice were selected randomly as control group from 55 healthy adult male Kunming mice,and the rest were used to establish chronic organophosphate poisoning cognitive impairment models by injecting omethoate 5 mg/kg subcutaneously every day for 4 weeks. Totally 40 successfully established models were randomly divid-ed into model group,AST group,edaravone group,LiCl group and AST+LiCl group with 8 in each. Morris wa-ter maze test was used to examine the learning and memory ability of mice. Contents of reactive oxygen spe-cies (ROS) in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). Activity of superoxide dismutase ( SOD) in hippocampus was measured by colorimetric assay. Morphology of hippocam-pus area was observed by HE staining. The distribution and expression of p-PI3K,p-Akt,p-GSK3β and p-CREB were determined by immunohistochemical staining ( IHC staining) and Western blot. Results The average escape latency of 5 days in each group was statistically significant (F=1662.147, P<0.05) . The av-erage escape latency of 5 days in AST+LiCl group was significantly lower than that in model group ( all P<0.05) and was lower than other treatment groups. Compared with the control group (0.087±0.007,0.084± 0.009,0.097±0.002,0.076±0.012),the hippocampal neuronal injury in model group was serious,the expres-sions of p-PI3K (0.032±0.008),p-Akt (0.03±0.006),p-GSK3β (0.028±0.007) and p-CREB (0.020± 0.008) was significantly lower ( all P<0.05) . The injuries of hippocampal neurons in AST+LiCl group were slightly lighter than that in model group,and the expression of p-PI3K (0.067±0.008),p-Akt (0.065± 0.005),p-GSK3β (0.068±0.009) and p-CREB (0.062±0.008) in hippocampus was significantly higher than that in model group ( all P<0.05) . Conclusion Combined AST and LiCL treatment exerts neuroprotec-tive effect on cognitive dysfunction induced by chronic organophosphate poisoning via up-regulating the ex-pression of Akt/GSK3β/CREB.