Infantile Spasms and Down Syndrome: A New Animal Model

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 substra...

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Bibliographic Details
Published in:Pediatric research Vol. 65; no. 5; pp. 499 - 503
Main Authors: Cortez, Miguel A, Shen, Liqing, Wu, Ying, Aleem, Ilyas S, Trepanier, Catherine H, Sadeghnia, Hamid R, Ashraf, Asim, Kanawaty, Ashlin, Liu, Chen-Chu, Stewart, Lee, Snead, O Carter
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01-05-2009
Lippincott Williams & Wilkins
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Summary: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 γ-butyrolactone, which induced acute epileptic extensor spasms (AEES) associated with epileptiform polyspike bursts and an electrodecremental response on the EEG. GABA B R-agonist-induced AEES were significantly reduced with vigabatrin, rodent ACTH fragment, valproic acid, ethosuximide, and CGP 35348. Porcine ACTH had no effect. GABA B R protein expression was significantly increased in the thalamus and medulla oblongata of Ts65D mice in comparison with wild-type controls. The GABA B R agonist-treated Ts65Dn mouse shows the unique clinical, electrographic, and pharmacologic signature of infantile spasms and represents a valid, acute model of this disorder. GABA B R-mediated mechanisms may contribute to the increased susceptibility of children with Down syndrome to infantile spasms.
ISSN:0031-3998
1530-0447
DOI:10.1203/PDR.0b013e31819d9076