title: Alterations in GABAA receptor alpha 1 and alpha 4 subunit mRNA levels in thalamic relay nuclei following absence-like seizures in rats.
abstract: Modification of GABAA receptor mRNA levels by seizure activity can regulate general neuronal excitability. The possibility of absence seizure-induced alteration in GABAA receptor alpha 1, alpha 4, beta 2, and gamma 2 subunit gene expression in thalamic relay nuclei was studied in a rat model of absence seizures induced by gamma-hydroxybutyric acid (GHB). We observed a marked increase in alpha 1 mRNA and a corresponding decrease in alpha 4 mRNA in thalamic relay nuclei 2-4 h after the onset of GHB-induced absence seizures (when the seizures were terminating). These changes were selective to these alpha isoforms as neither beta 2 nor gamma 2 mRNA changed following seizures and occurred only in thalamic relay nuclei but not in hippocampus, a structure from which absence seizures do not evolve. The alterations in alpha 1 and alpha 4 mRNA persisted until about 12 h, and by 24 h after the seizure-onset the mRNA levels normalized. Blocking GHB-seizures produced no change in the levels of alpha 1 and alpha 4 mRNA in thalamic relay nuclei, suggesting that seizures themselves were responsible for mRNA alterations. In order to determine if absence seizure-induced changes in alpha 1 and alpha 4 mRNA had any physiological significance, GHB was readministered in rats 6 and 24 h after the onset of seizures. The total duration of GHB-seizures was found to be significantly decreased when GHB was readministered at 6 h but not 24 h after the seizure-onset. These results suggest that absence seizures regulate GABAA receptor alpha 1 and alpha 4 gene expression in thalamic relay nuclei as a compensatory mechanism by which absence seizures are terminated.
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Canada. pradeep.banerjee@mailhub.sickkids.on.ca
authors.forename: P K
authors.initials: PK
authors.lastname: Banerjee
authors.forename: N J
authors.initials: NJ
authors.lastname: Tillakaratne
authors.forename: S
authors.initials: S
authors.lastname: Brailowsky
authors.forename: R W
authors.initials: RW
authors.lastname: Olsen
authors.forename: A J
authors.initials: AJ
authors.lastname: Tobin
authors.forename: O C
authors.initials: OC
authors.lastname: Snead
mesh_terms: D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics*; D013788:Thalamus / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018756:GABA Antagonists; D018757:GABA Modulators; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C066430:CGP 35348; D015107:4-Butyrolactone