Abstracts

RATIONALE: Glutamate is a predominantly excitatory neurotransmitter in the mammalian central nervous system. We previously reported the abnormal glutamate release during the seizure following kindling. GLAST and GLT-1 are the astrocytic glutamate transporters, highly concentrated in the cerebellum and the telencephalon, respectively. It is seldom that GLT-1 knockout mouse survives more than 3 weeks. We have investigated whether stages of amygdala kindling in knockout(KO) mouse deficient GLT-1 are the same as those of wild mice and whether there is secondary epileptogenesis.
METHODS: Electrodes are implanted into the basolateral amygdala (B2.0,L3.0,H-4.0-4.5) in GLT-1 KO mouse(Body weight: BW 13g in 2 month) and the control C57BL/6J mice(BW29-32g) under the anesthesia(pentobarbital 30mg/kg). Once-daily stimulation of biphasic square pulse (1msec, 60 Hz, 50-100microA]A, 2sec) was applied through the stimulation electrodes. After the experiment the brain was perfused by the buffered formalin and examined histologically .
RESULTS: The behavioral characteristics of GLT-1 KO mouse are peculiar, as displayed in a tendency to hide inside the litter and isolate itself from the other. The number of stimulations to induce behavioral changes of the kindling in control mice were: 1) arrest of behavior: 1.9, 2) head nodding 3.7, 3) forelimb clonus: 6.9, 4) both forelimb clonus with rearing: 8.9, 5) tonic generalized convulsion with elevation of tail, falling with GTC 12.4. In the case of GLT-1 KO mouse, the 1st stimulation induced facial movement and forlimb clonus. The 2nd stimulation induced rearing. The 5th stimulation induced brief GTC and running. The 9th Stimulation induced repeated rearing . Before the stimulation, EEG was monitored more than 24 hours. There was no spontaneous spike. The number of epileptiform spontaneous discharges after the stimulation was greater than that of control until 8-9 stimulations. Later the number of spikes decreased. The 9th stimulation induced the repeated seizure activity localized at the contralateral amygdala on the EEG. The duration of afterdischarge did not become longer except in the case of repeated seizures.
CONCLUSIONS: We have investigated the kindling in the astroglial Glutamate transporte(rGLT-1) deficient mouse. The results were an early development of kindling. The number of spikes of GLT-1 KO mouse was greater than that of control. Repeated seizure activities were recognized in the contralateral amygdala. These findings suggest to us that the secondary epileptogenesis may be accerelated in the GLT-1 KO mouse. The astroglial glutamate transporter in the telencephalon may have an important role in inhibiting secondary epileptogenesis.