Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder.
Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder.
复制标题
作者：
神经元迁移障碍会导致大脑新皮质畸形，极大地增加癫痫发作的风险。神经元迁移障碍引起的畸形是否可以通过重新激活细胞迁移来减少，以及这种修复是否可以降低癫痫发作的风险，目前还没有得到测试。在这里，我们展示了，在由DCX宫内RNAi产生的皮质下带状异位(SBH)的大鼠模型中，出生后重新表达DCX可以刺激位置异常的神经元迁移。以这种方式重新开始迁移既减少了新皮质畸形，又恢复了神经元模式。我们进一步发现，降低SBH的能力在出生后早期发育有一个关键期。此外，出生后的干预将惊厥诱导的癫痫阈值降低到与无畸形对照组相似的水平。这些结果表明，神经元迁移障碍可能最终可以通过重新启动发育程序来治疗，以减少皮质畸形的大小和降低癫痫发作的风险。
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 RNAi of Dcx, that aberrantly positioned neurons can be stimulated to migrate by re-expressing Dcx after birth. Re-starting migration in this way both reduces neocortical malformations and restores neuronal patterning. We find further that the capacity to reduce SBH has a critical period in early postnatal development. Moreover, intervention after birth reduces convulsant-induced seizure threshold to levels similar to that of malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by re-engaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk.
登录
查看更多内容
影响因子：
14.5
作者：
D'Agostino, MD;Bernasconi, A;Andermann, E
通讯作者：
Andermann, E
影响因子：
3.6
作者：
Baraban, Scott C.
通讯作者：
Baraban, Scott C.
影响因子：
19.7
作者：
BARKOVICH, AJ;JACKSON, DE;BOYER, RS
通讯作者：
BOYER, RS
影响因子：
2.2
作者：
Baraban, SC;Schwartzkroin, PA
通讯作者：
Schwartzkroin, PA
影响因子：
16.2
作者：
Koizumi, H;Tanaka, T;Gleeson, JG
通讯作者：
Gleeson, JG