Canna~Fangled Abstracts

Loss of Cannabinoid CB 1 Receptors Induces Cortical Migration Malformations and Increases Seizure Susceptibility.

By October 26, 2016 No Comments
Cereb Cortex. 2016 Oct 5:1-15. doi: 10.1093/cercor/bhw309. [Epub ahead of print]Díaz-Alonso J1,2,3, de Salas-Quiroga A1,2, Paraíso-Luna J1,2, García-Rincón D1,2, Garcez PP4,5, Parsons M6, Andradas C1,7, Sánchez C1,7, Guillemot F8, Guzmán M1,2, Galve-Roperh I1,2.


pm-2-site-207Neuronal migration is a fundamental process of brain development, and its disruption underlies devastating neurodevelopmental disorders. The transcriptional programs governing this process are relatively well characterized. However, how environmental cues instruct neuronal migration remains poorly understood. Here, we demonstrate that the cannabinoid CB 1 receptor is strictly required for appropriate pyramidal neuron migration in the developing cortex. Acute silencing of the CB 1 receptor alters neuronal morphology and impairs radial migration. Consequently, CB 1 siRNA-electroporated mice display cortical malformations mimicking subcortical band heterotopias and increased seizure susceptibility in adulthood. Importantly, rescuing the CB 1 deficiency-induced radial migration arrest by knockdown of the GTPase protein RhoA restored the hyperexcitable neuronal network and seizure susceptibility. Our findings show that CB 1 receptor/RhoA signaling regulates pyramidal neuron migration, and that deficient CB 1 receptor signaling may contribute to cortical development malformations leading to refractory epilepsy independently of its canonical neuromodulatory role in the adult brain.


endocannabinoid system; epileptogenesis; radial migration; small GTPases; subcortical band heterotopia

PMID: 28334226


DOI: 10.1093/cercor/bhw309
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