Amygdala-kindled and pentylenetetrazole-induced seizures in glutamate transporter GLAST-deficient mice.
The glutamatergic system has been shown to be important for the induction of epileptiform activity and the development of epileptogenesis. To investigate the role of the astroglial glutamate transporter GLAST in epileptogenesis, we examined amygdala (AM)-kindled and pentylenetetrazole (PTZ)-induced seizures in GLAST-deficient mice (GLAST(-/-)) and compared them to those observed in wild-type mice (GLAST(+/+)) and maternal C57Black6/J (C57) mice. AM-kindling resulted in no significant differences in afterdischarge threshold or in the seizure responses induced by first stimulation between these groups. In addition, although no significant differences were seen in kindled seizure development, the generalized seizure duration of AM-kindled seizures in GLAST(-/-) mice was significantly prolonged (approximately 35%) compared with that of C57 mice. Furthermore, GLAST(-/-) mice showed more severe stages of PTZ-induced seizures than GLAST(+/+) mice, and the latency to the onset of seizures was significantly shorter for the mutant mice. These results indicate that GLAST is one of factors determining seizure susceptibility.
Watanabe
T
T
Department of Neuropsychiatry, Faculty of Medicine, Kagawa Medical University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. 52takemi@kms.ac.jp
Morimoto
K
K
Hirao
T
T
Suwaki
H
H
Watase
K
K
Tanaka
K
K
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D027322:Amino Acid Transport System X-AG; D000679:Amygdala / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000502:physiology; D003292:Convulsants; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D007696:Kindling, Neurologic / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010433:Pentylenetetrazole; D011930:Reaction Time / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D003292:Convulsants; D010433:Pentylenetetrazole