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Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder.

Authors: Manent, Jean-Bernard  Wang, Yu  Chang, Yoonjeung  Paramasivam, Murugan  LoTurco, Joseph J 
Citation: Manent JB, etal., Nat Med. 2009 Jan;15(1):84-90. doi: 10.1038/nm.1897. Epub 2008 Dec 21.
Pubmed: (View Article at PubMed) PMID:19098909
DOI: Full-text: DOI:10.1038/nm.1897

Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNA interference of the Dcx gene, that aberrantly positioned neurons can be stimulated to migrate by reexpressing Dcx after birth. Restarting migration in this way both reduces neocortical malformations and restores neuronal patterning. We further find that the capacity to reduce SBH continues into early postnatal development. Moreover, intervention after birth reduces the convulsant-induced seizure threshold to a level similar to that in malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by reengaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk.

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CRRD Object Information
CRRD ID: 12904725
Created: 2017-05-19
Species: All species
Last Modified: 2017-05-19
Status: ACTIVE



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