Journal
NATURE MEDICINE
Volume 15, Issue 1, Pages 84-90Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1897
Keywords
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Funding
- US National Institutes of Health [MH056524, NS062416]
- Jerome Lejeune foundation
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD055655] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH056524, R29MH056524] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS062416] Funding Source: NIH RePORTER
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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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