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Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus.

Authors: Nosten-Bertrand, Marika  Kappeler, Caroline  Dinocourt, Céline  Denis, Cécile  Germain, Johanne  Phan Dinh Tuy, Françoise  Verstraeten, Soraya  Alvarez, Chantal  Métin, Christine  Chelly, Jamel  Giros, Bruno  Miles, Richard  Depaulis, Antoine  Francis, Fiona 
Citation: Nosten-Bertrand M, etal., PLoS One. 2008 Jun 25;3(6):e2473. doi: 10.1371/journal.pone.0002473.
Pubmed: (View Article at PubMed) PMID:18575605
DOI: Full-text: DOI:10.1371/journal.pone.0002473

Patients with Doublecortin (DCX) mutations have severe cortical malformations associated with mental retardation and epilepsy. Dcx knockout (KO) mice show no major isocortical abnormalities, but have discrete hippocampal defects. We questioned the functional consequences of these defects and report here that Dcx KO mice are hyperactive and exhibit spontaneous convulsive seizures. Changes in neuropeptide Y and calbindin expression, consistent with seizure occurrence, were detected in a large proportion of KO animals, and convulsants, including kainate and pentylenetetrazole, also induced seizures more readily in KO mice. We show that the dysplastic CA3 region in KO hippocampal slices generates sharp wave-like activities and possesses a lower threshold for epileptiform events. Video-EEG monitoring also demonstrated that spontaneous seizures were initiated in the hippocampus. Similarly, seizures in human patients mutated for DCX can show a primary involvement of the temporal lobe. In conclusion, seizures in Dcx KO mice are likely to be due to abnormal synaptic transmission involving heterotopic cells in the hippocampus and these mice may therefore provide a useful model to further study how lamination defects underlie the genesis of epileptiform activities.


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CRRD Object Information
CRRD ID: 12904723
Created: 2017-05-19
Species: All species
Last Modified: 2017-05-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.