The Relationship Between MARK1Expression And Mossy Fiber Sprouting Of Hippocampus In PTZ Kindling Model

ObjectTo explore the role of MARK1in mossy fiber sprouting, we investigated the dynamic changes of the microtubule affinity-regulating kinase-1(MARK1) in hippocampus of PTZ kindling model and the relationship between the expression of MARK1and mossy fiber sprouting. Our findings in this aspect may provide new ideas for the treatment of epilepsy.Methods90healthy male SD rats were divided randomly into normal control(30) and PTZ kindling model(60) groups. The Rats of PTZ model group was intraperitoneally injected PTZ(30mg/kg)once every day. The control group received0.9%saline instead of PTZ once every day at the same time. Then the two groups were randomly divided into five subgroups according to3days,1week,2weeks,4weeks,6weeks after the first PTZ injection. Every subgroup was then divided into two teams randomly again. The MARK1was analyzed in the various subfields of hippocampus by immunohistochemistry at different time points in one team. Timm staining was scored at each time point in the CA3region and dentate gyrus of hippocampus in another team.Results1.Animal modelAfter21-28days (23.6±2.0days),95.8%animals were kindled and5.0%animals were dead. Seizure-form discharges were recorded on the EEG in the kindled rats and spontaneous seizures were observed in these rats. Neither seizure nor seizure-form discharge on the EEG was discovered in the nomal control group.2. Dynamic changes of hippocampal mossy fiber sprouting(1)PTZ group:In the CA3region, Timm scores were significantly higher, compared with the normal control group at different times(P<0.05). With daily injection of PTZ, the Timm scores in the CA3region increased from3days gradually, and reached the peak after two weeks’injection, and then maintained high level until the6th week.(2)There was no significant difference in the scores in supragranular region of the dentate gyrus at each time point in neither the PTZ group nor the control group.(3) In the control group, Timm scores in the CA3region and supragranular of the DG had no significant difference at each time point.3. Dynamic changes of MARK1(1)The PTZ group:Compared with the nomal control group, MARK1protein in hippocampus of the PTZ group began to decrease from3days, and continued to fall until the6th week. The expression of MARK1in CA1region in the PTZ group was significantly decreased at4th and6th weeks compared with the normal control group(P<0.05). In CA3region, the expression in PTZ group was significantly decreased at1st week compared with the normal control group(P<0.05), especially in the2nd%4th and6th weeks. While in both DG and hilar regions, their expression at each time point in the PTZ group were significantly decreased compared with the nomal control group(P<0.05or P<0.01).(2)The normal control group:the dynamic changes of MARK1in different hippocampus regions had no statistical significance at each time point.4. The relationship between hippocampal mossy fiber sprouting and expression of MARK1in the PTZ groupIn the PTZ group, the changes of hippocampal mossy fiber sprouting scores had a negative correlation with the dynamic changes of MARK1protein in CA3region,the correlational coefficient r=-0.879, P<0.01.Conclusion1. The decreased expression of MARK1in rats’hippocampus of PTZ kindling model was related with mossy fiber sprouting.