RT Journal Article
T1 Loss of cannabinoid CB1 receptors induces cortical migration malformations and increases seizure susceptibility
A1 Díaz Alonso, Javier
A1 Salas Quiroga, Adán de
A1 Paraíso Luna, Juan
A1 García Rincón, Daniel
A1 Garcez, Patricia P.
A1 Parsons, Maddy
A1 Andradas Arias, Clara
AB Neuronal 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 CB1 receptor is strictly required for appropriate pyramidal neuron migration in the developing cortex. Acute silencing of the CB1 receptor alters neuronal morphology and impairs radial migration. Consequently, CB1 siRNAelectroporated mice display cortical malformations mimicking subcortical band heterotopias and increased seizure susceptibility in adulthood. Importantly, rescuing the CB1 deficiency-induced radial migration arrest by knockdown of the GTPase protein RhoA restored the hyperexcitable neuronal network and seizure susceptibility. Our findings show that CB1 receptor/RhoA signaling regulates pyramidal neuron migration, and that deficient CB1 receptor signaling may contribute to cortical development malformations leading to refractory epilepsy independently of its canonical neuromodulatory role in the adult brain.
PB Oxford University Press
SN 1047-3211, ESSN: 1460-2199
YR 2017
FD 2017-11
LK https://hdl.handle.net/20.500.14352/18394
UL https://hdl.handle.net/20.500.14352/18394
LA eng
NO Ministerio de Economía y Competitividad (MINECO)/FEDER
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 9 abr 2025