Dynamic Changes Of Cdk5 Activity And Its Correlations With Mossy Fiber Sprouting Of Rat Hippocampal In PTZ Kindling Model

Object To observe the changes of Cdk5 activity in hippocampus associated with the changes of hippocampal mossy fiber sprouting in the pentylenetetrazole (PTZ) kindling model and to investigate the role of Cdk5 in 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 were scored at different time in the CA3 region of hippocampus and dentate gyrus. The Cdk5 activity was analyzed at different time with a liquid scintillation counter respectively.Results1. Animal modelAfter 21-28 injections (26.1±1.6 days), 91.7% animals were kindled and 3.3% were dead. 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 points. There were no distinct differences in both CA3 region and supra- granular region of the control group at different time points.3. Dynamic changes of Cdk5 activityThe levels of Cdk5 activity in hippocampus was significantly higher at the PTZ treated groups of 3d, 1w, 2w, and 4w than that of controls. Thereafter, the activity decreased to the levels of controls. The levels of Cdk5 activity in lobus frontalis had no significance at the PTZ treated groups of all the time points as well as that of controls. There were no distinct differences in both hippocampus and lobus frontalis of the control group at different time points.ConclusionsCdk5 may play a role in epileptogenesis through influencing moss fiber sprouting by its elevated activity.