title: Spontaneous epileptic manifestations in a DCX knockdown model of human double cortex.
abstract: Previous reports indicate that in utero knockdown of doublecortin (DCX) results in the genesis of a subcortical heterotopia reminiscent of the doublecortex observed in female patients with DCX mutations. It has also been shown that these rats display an increased susceptibility to convulsant agents and increased cortical neurons excitability; but it is presently unknown whether they display spontaneous seizures. Furthermore, the link between the size of heterotopia and the clinical manifestation remained to be elucidated. Using video-electrocorticogram recordings, we now report that DCX knockdown induces frequent spontaneous seizures commonly associated with myoclonic jerks in adult rats. Surprisingly, epilepsy occurred even in rats with very small subcortical heterotopias, as revealed by histological analysis of recorded animals. Moreover, the severity of the epileptic manifestations was positively correlated with both the size of the subcortical heterotopia and the age of recorded animals; thus, epileptic features were not detected in immature affected rats. In conclusion, our data demonstrate for the first time that subtle alterations can yield epilepsy and reveal a strong correlation between thicknesses of subcortical heterotopia, age of affected individuals and clinical impairment.
authors.affiliation: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Damien
authors.initials: D
authors.lastname: Lapray
authors.forename: Irina Y
authors.initials: IY
authors.lastname: Popova
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kindler
authors.forename: Isabel
authors.initials: I
authors.lastname: Jorquera
authors.forename: Hélène
authors.initials: H
authors.lastname: Becq
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Manent
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
authors.forename: Alfonso
authors.initials: A
authors.lastname: Represa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D009479:Neuropeptides / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C000714328:DCX protein, human; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides