The Neuroprotective Effects Of Astaxanthin On Cognitive Dysfunction By Chronic Omethoate-poisoned Mice

Objective: To investigate the neuroprotective effects and potential mechanism of astaxanthin(AST)on cognitive dysfunction by chronic omethoate-poisoned mice.Methods: 8 mice were selected randomly as control group from 55 healthy adult male kunming mice,and the rest 47 mice were used to establish mouse model of chronic omethoate poison(OP)-induced cognitive dysfunction by injected omethoate 5 mg/kg subcutaneously every day for 4 weeks.Totally 40 successfully established models were randomly divided into model group,AST group,edaravone group,Li Cl group and AST+Li Cl group with 8 in each.AST was dissolved in peanut oil to 1 mg/m L and administrated daily at 50 ?g/g/day by gavage for 4 weeks.Edaravone was administrated at 3 mg/kg by intraperitoneal injection daily for continuous 4 weeks.Li Cl was administrated at 2 mmol/kg by intraperitoneal injection every other day for 4 weeks.AST+Li Cl treatment was performed by gavage for AST and intraperitoneal injection of Li Cl,respectively.Mice in the control and model groups were given equal volume of peanut oil by gavage.Spatial learning and memory were assessed by the Morris water maze assay.Contents of reactive oxygen species(ROS)in hippocampus was measured by enzyme-linked immunosorbent assay(ELISA).Activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-PX)in hippocampus were measured by colorimetric assay.The morphology,pathology,and the apoptotic cells in the hippocampus were monitored by hematoxylin eosin,Congo red,and TUNEL stains,respectively.The activation of p-PI3 K,p-Akt,p-GSK3? and p-CREB were evaluated by both immunohistochemical staining and western blotting analyses.Results : After OPs poisoning,the abnormal behavior showed in model group mice,manifesting decline of learning and memory ability.ROS contents increased significantly,however,the activities of SOD and GSH-PX were decreased apparently(all P<0.05),in which damaged neurons appear,and amyloid deposition was obviously observed in peripheral vascular wall.The number of neuronal apoptosis in model group increased significantly than that in control group(P < 0.05).The expressions of p-PI3 K,p-Akt,p-GSK3? and p-CREB were decreased significantly than those in control group(all P<0.05).The learning and memory ability in AST group improved apparently,the contents of ROS was obviously decreased,and SOD and GSH-PX were significantly increased.Neuronal damage reduced in hippocampus,and number of apoptotic cells as well as deposition of amyloid decreased significantly compared with model group(P<0.05).The expressions of p-PI3 K,p-Akt,p-GSK3? and p-CREB were significantly higher than those in model group(all P<0.05).Conclusion: AST can protect cognitive function against chronic omethoate poisoning by up-regulating the expression of Akt/GSK3?/CREB signaling pathway.