Dynamic Changes Of GSK-3β Activity And Its Correlations With Mossy Fiber Sprouting In Hippocampus Of PTZ Kindling Rat Model

Object To observe the changes of GSK-3βactivity in hippocampus associated with the changes of hippocampal mossy fiber sprouting in the pentylenetetrazole (PTZ) kindling model and to investigate the role of GSK-3βin epileptogenesis.Methods 120 healthy male Sprague-Dawley rats were divided randomly into control and PTZ treated groups. The PTZ treated groups were intraperitoneally injected PTZ (30mg/kg) every 24 hours and were stopped injection once kindled. The control groups received 0.9% saline injections instead of PTZ at the same time. Seizure manifestations were evaluated according to Racine and EEG At 3d, 1w, 2w, 4w, 6w after the first PTZ injection, Timm staining was scored at different time in the CA3 region of hippocampus and dentate gyrus. By using activity assay, GSK-3βactivity of hippocampus was analyzed at different time point.Results1. Animal modelAfter 21-28 injections (26.1±1.6 days), 91.7% animals were kindled. Seizure-form discharges were recorded on the EEG in the kindled rats while the control rats and unkindled rats have neither seizures nor seizure-form discharges on the EEG.2. Changes of hippocampal mossy fiber sproutingWith daily PTZ application, the Timm scores in the CA3 region, which gradually increased from 3d to 2w, were significantly higher than that in controls at different time and maintained high levels in the 4w and 6w groups. There were no significant differences in supragranular region between the PTZ treated group and the control group at different time point.3. Changes of GSK-3βactivityGSK3βis widely expressed in cerebral cortex, subcortex structure, cerebellum, brain stem. The expression level is much higher in hippocampus. The activity levels of GSK-3βin hippocampus were significantly higher at the PTZ treated groups of 3d, 1w, 2w, and 4w than that of controls. Thereafter, the expression decreased to the levels of controls. The activity levels of GSK-3βin lobus frontalis had no significance at the PTZ treated groups of 3d, 1w, 2w, 4w and 6w as well as that of controls.ConclusionsIn PTZ kindling rat model, The up-regulation of GSK-3βactivity in hippocampus participated in the procession of mossy fiber sprouting, promoted the occurrence of epilepsy.