Mossy Fiber Synaptic Reorganization of Dentate Gyrus by Pentylenetetrazol Kindling Rats

ABSTRACT

Recent studies have revealed that mossy fiber(MF) axons of dentate granule cells undergo synaptic reorganization in both electrical kindling models of temporal lobe epilepsy (TLE) and human TLE. This synaptic reorganization has been demonstrated by Timm histochemistry which selectively labels synaptic terminals of MF because of unusually high zinc content. Of MF. In electrical kindling model and human TLE Timm granules were distributed throughout the supragranular layer of dentate gyrus where they are not normally present. These supragranular Timm granules are regarded as MF synaptic reorganization. Kindling model of generalized epilepsy can be made by repeated intraperitoneal injections of subconvulsive dosage of pentylenetetrazol (PTZ). The present study is designed to test the hypothesis that MF synaptic reorganization might be developed in PTZ kindling model In this study, the supragranular Timm granules by Timm histochemistry were scored and depth EEG was recorded in dentate gyrus of various stages of PTZ kindling rats. The scores of supragranular Timm granules were 0. 33+0.17 in stage I seizure (n=9) ; 0. 38 + 0. 14 in stage II seizure (n=13) ; 0. 44 + 0. 18 in stage III seizure (n=9) ; 1. 40+0.16 in 3 consecutive or total 5-7 stage TV or V seizure (n=10) ; 1. 86+ 0.26 in 7-10 consecutive or total 10-15 stage IV or V seizure (n=7) ; 2.50+0.22 in 1215 consecutive or total 20-30 stage IV or V seizure (n=6) ; and 0. 30+0.15 in salinen controls (n=lo). Statistical analysis showed the supragranular Timm scorwere significantly higher in stage IV or V seizure than in control and in stage 1, I or, I seizure (p<0.05 ), and tended to increase with increasing numbers of stage IV or V seizure. Depth EEG recording from dentate gyrus showed 6-9Hz rhythmic waves in saline injected control, single or polyspikes or normal waves during stage I seizure, 4-6Hz slow waves or spike-waves complexes lasting 1-2 seconds during stage II seizure, 4-6Hz slow waves or spike-waves complexes lasting 3-6 seconds during stage III seizure, 8-15Hz spikes lasting over 10 seconds during stage IV seizure and 10-30HZ spikes lastmg over 20 seconds durmg stage V seizure The results demonstrate the development of MF synaptic reorganization and a sound correlation between MF synaptic reorganization and the progression of the kindlmg phenomenon in PTZ kindling models. These findings suggest that MF synaptic reorganization might be a critical event underlying the development and . Maintenance of kindling phenomenon and epileptic state.