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

Nature medicine | Jan 8, 2009

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.

Pubmed ID: 19098909 RIS Download

Mesh terms: Animals | Animals, Genetically Modified | Cell Movement | Classical Lissencephalies and Subcortical Band Heterotopias | Disease Models, Animal | Female | Gene Knockdown Techniques | Genetic Predisposition to Disease | Genetic Therapy | Malformations of Cortical Development, Group II | Microtubule-Associated Proteins | Models, Biological | Neurons | Neuropeptides | Pregnancy | RNA Interference | Rats | Seizures | Severity of Illness Index

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Associated grants

  • Agency: NIMH NIH HHS, Id: MH056524
  • Agency: NINDS NIH HHS, Id: NS062416
  • Agency: NICHD NIH HHS, Id: R01 HD055655
  • Agency: NICHD NIH HHS, Id: R01 HD055655-02
  • Agency: NIMH NIH HHS, Id: R01 MH056524
  • Agency: NINDS NIH HHS, Id: R21 NS062416
  • Agency: NINDS NIH HHS, Id: R21 NS062416-01A1

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