Infantile Spasms and Down Syndrome: A New Animal Model
| Autor: | Ilyas S. Aleem, Hamid Reza Sadeghnia, Liqing Shen, O. Carter Snead, Catherine H. Trepanier, Ying Wu, Chen Chu Liu, Miguel A. Cortez, Asim Ashraf, Ashlin Kanawaty, Lee S. Stewart |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Baclofen
medicine.medical_specialty Pathology Down syndrome Time Factors Genotype Thalamus Electroencephalography Vigabatrin Mice chemistry.chemical_compound Organophosphorus Compounds 4-Butyrolactone Internal medicine medicine Animals Humans GABA Agonists Valproic Acid medicine.diagnostic_test business.industry Brain Infant Receptors GABA-A medicine.disease Mice Mutant Strains Disease Models Animal Phenotype Endocrinology Ethosuximide Receptors GABA-B chemistry Pediatrics Perinatology and Child Health Medulla oblongata Anticonvulsants Down Syndrome business Spasms Infantile medicine.drug |
| Zdroj: | Pediatric Research. 65:499-503 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/pdr.0b013e31819d9076 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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