P38MAPK/ATF2 Signaling Pathway Involves In PND Of Mice

Objective: to investigate whether P38MAPK/ATF2 signaling pathway involves in PND of miceMethods: 1.Observations of hippocampal neuroinflammation and neuronal apoptosis in aged PND mice 16-month-old healthy female C57 mice were randomly divided into control group(CON)and surgical group(SUR).Mice in the SUR group were received internal fixation of tibial plateau fracture under isoflurane anesthesia.Mice in the CON group didn’t receive surgery.Then mice in each group were subjected to behavioral tests on the 1st,3rd,and 7th day after surgery,Open-field testing(OFT)was performed to evaluate the locomotor activity of the mice,learning and memory abilities were measured by Morris Water Maze(MWM)and Fear Conditioning Test(FCT),some mice were sacrificed after each behavioral tests.Western Blot and PCR were employed to detect the expression levels of hippocampal IL-1β,TNF-α,caspase-3,bax,bcl-2 and P38 pathways in mice.The activated microglia and surviving neurons in the CA1 area of the hippocampus were assessed by immunofluorescence and Nissl staining.2.Effect of SB239063 on perioperative neurocognitive of aged mice 16-month-old healthy female C57 mice were randomly divided into surgery group(SUR)and surgery+SB239063 group(SB),Mice in the SUR and SB groups were received internal fixation of tibial plateau fracture under isoflurane anesthesia.SB group mice were administered SB239063(15mg/kg)by intraperitoneally 1 hour before and 6 hours after surgery.Mice in each group received behavioral tests on the 1st,3rd,and 7th days after surgery,OFT、MWM and FCT were performed to assess the locomotor activity,learning and memory of the mice.Then the mice were sacrificed,Western blot and PCR were employed to detect the expression levels of hippocampal p-P38/ATF2,IL-1β,TNF-α,caspase-3,bax,bcl-2 in mice.The activated microglia and surviving neurons in the hippocampal CA1 region of mice were observed by immunofluorescence and Nissl staining.Results: 1.Observations of hippocampal neuroinflammation and neuronal apoptosis in aged PND mice Compared with CON group,mice in SUR group had longer latency period and fewer times of crossing the platform in the MWM,and shortened freezing time in the FCT(P<0.05).Western blot and PCR showed that the expression levels of IL-1β,TNF-α,caspase-3,and bax in the hippocampus of the SUR group mice increased,while the expression of bcl-2 decreased(P<0.01);the expression of p-P38 in the P38 pathway increased,while the expression of ATF2 decreased(P<0.05).Immunofluorescence and Nissl staining showed that microglia activation and neuronal loss increased in the CA1 area of the hippocampus.2.Effect of SB239063 on perioperative neurocognitive of aged mice Compared with SUR group,mice in SB group had shorter latency and more times of crossing the platform in the MWM,and increased freezing time in the FCT(P<0.05).Western blot and PCR detected decreased expression levels of p-P38,IL-1β,TNF-α,caspase-3 and bax,and increased expression levels of ATF-2 and bcl-2 in the hippocampus of SB group(p<0.05).Immunofluorescence and Nissl staining showed that microglial activation and neuronal loss were reduced in the CA1 area of the hippocampus.Conclusion: Inhibition of the P38MAPK/ATF2 signaling pathway is able to attenuate hippocampal neuroinflammation and neuronal apoptosis in aged PND mice,thus improve the perioperative cognitive function of mice.