Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus.
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...
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2008
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oai:doaj.org-article:aff3bab36c654b1b90feacad4d89878a2021-11-25T06:11:54ZEpilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus.1932-620310.1371/journal.pone.0002473https://doaj.org/article/aff3bab36c654b1b90feacad4d89878a2008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18575605/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Patients 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.Marika Nosten-BertrandCaroline KappelerCéline DinocourtCécile DenisJohanne GermainFrançoise Phan Dinh TuySoraya VerstraetenChantal AlvarezChristine MétinJamel ChellyBruno GirosRichard MilesAntoine DepaulisFiona FrancisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 6, p e2473 (2008) |
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Medicine R Science Q Marika Nosten-Bertrand Caroline Kappeler Céline Dinocourt Cécile Denis Johanne Germain Françoise Phan Dinh Tuy Soraya Verstraeten Chantal Alvarez Christine Métin Jamel Chelly Bruno Giros Richard Miles Antoine Depaulis Fiona Francis Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| description |
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. |
| format |
article |
| author |
Marika Nosten-Bertrand Caroline Kappeler Céline Dinocourt Cécile Denis Johanne Germain Françoise Phan Dinh Tuy Soraya Verstraeten Chantal Alvarez Christine Métin Jamel Chelly Bruno Giros Richard Miles Antoine Depaulis Fiona Francis |
| author_facet |
Marika Nosten-Bertrand Caroline Kappeler Céline Dinocourt Cécile Denis Johanne Germain Françoise Phan Dinh Tuy Soraya Verstraeten Chantal Alvarez Christine Métin Jamel Chelly Bruno Giros Richard Miles Antoine Depaulis Fiona Francis |
| author_sort |
Marika Nosten-Bertrand |
| title |
Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| title_short |
Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| title_full |
Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| title_fullStr |
Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| title_full_unstemmed |
Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| title_sort |
epilepsy in dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/aff3bab36c654b1b90feacad4d89878a |
| work_keys_str_mv |
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