Downregulation of kainate receptors in the hippocampus following repeated seizures in immature rats.
There are significant differences in seizure-induced sequelae between the immature and mature brain. We have previously demonstrated that repeated doses of the chemoconvulsant kainic acid is associated with a progressive increase in severity of seizures in adult animals while in immature rats the opposite occurs; seizure intensity decreases with subsequent doses of kainic acid. Likewise, repeated kainic acid seizures causes severe hippocampal damage in mature rats while in the immature brain serial administration of kainic acid causes no demonstrable cell loss. Here we show that recurrent kainic acid seizures in immature rats are associated with a downregulation of kainate receptor binding. No histological damage was noted in any of the rats exposed to recurrent seizures. Furthermore, when tested for visual-spatial memory immature rats with recurrent kainate seizures did not differ from controls. The downregulation of KA receptors following repeated exposure to KA suggests that the decrease in glutamate receptor density might account in part for the observed lack of neuronal loss and decrease in seizure intensity in these animals.
Tandon
Pushpa
P
Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital, Boston, MA 02115, USA.
Yang
Yili
Y
Stafstrom
Carl E
CE
Holmes
Gregory L
GL
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D007608:Kainic Acid / Q000494:pharmacology; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D009498:Neurotoxins; D018092:Kainic Acid Receptors