title: Infantile spasms and Down syndrome: a new animal model.
abstract: Infantile spasms is a catastrophic childhood seizure disorder for which few animal models exist. Children with Down syndrome are highly susceptible to infantile spasms. The Ts65Dn mouse is a valid model for Down syndrome; therefore, we tested the hypothesis that the Ts65Dn mouse represents a substrate for an animal model of infantile spasms. The baseline of naïve Ts65Dn mice showed spontaneous spike-and-wave discharges, a pattern that worsened with baclofen and gamma-butyrolactone, which induced acute epileptic extensor spasms (AEES) associated with epileptiform polyspike bursts and an electrodecremental response on the EEG. GABABR-agonist-induced AEES were significantly reduced with vigabatrin, rodent ACTH fragment, valproic acid, ethosuximide, and CGP 35348. Porcine ACTH had no effect. GABABR protein expression was significantly increased in the thalamus and medulla oblongata of Ts65D mice in comparison with wild-type controls. The GABABR agonist-treated Ts65Dn mouse shows the unique clinical, electrographic, and pharmacologic signature of infantile spasms and represents a valid, acute model of this disorder. GABABR-mediated mechanisms may contribute to the increased susceptibility of children with Down syndrome to infantile spasms.
authors.affiliation: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cortez
authors.forename: Liqing
authors.initials: L
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Ilyas S
authors.initials: IS
authors.lastname: Aleem
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Trepanier
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Sadeghnia
authors.forename: Asim
authors.initials: A
authors.lastname: Ashraf
authors.forename: Ashlin
authors.initials: A
authors.lastname: Kanawaty
authors.forename: Chen-Chu
authors.initials: CC
authors.lastname: Liu
authors.forename: Lee
authors.initials: L
authors.lastname: Stewart
authors.forename: O Carter
authors.initials: OC
authors.lastname: Snead
mesh_terms: D015107:4-Butyrolactone; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001418:Baclofen; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D004569:Electroencephalography; D005013:Ethosuximide / Q000494:pharmacology; D018755:GABA Agonists; D005838:Genotype; D006801:Humans; D007223:Infant; D051379:Mice; D008817:Mice, Mutant Strains; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010641:Phenotype; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D013036:Spasms, Infantile / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology; D020888:Vigabatrin / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D018755:GABA Agonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005013:Ethosuximide; D014635:Valproic Acid; C066430:CGP 35348; D020888:Vigabatrin; D001418:Baclofen; D015107:4-Butyrolactone