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Loss of cannabinoid CB1 receptors induces cortical migration malformations and increases seizure susceptibility

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Díaz Alonso, Javier and Salas Quiroga, Adán de and Paraíso Luna, Juan and García Rincón, Daniel and Garcez, Patricia P. and Parsons, Maddy and Andradas Arias, Clara (2017) Loss of cannabinoid CB1 receptors induces cortical migration malformations and increases seizure susceptibility. Cerebral Cortex, 27 (11). pp. 5303-5317. ISSN 1047-3211, ESSN: 1460-2199

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Official URL: https://academic.oup.com/cercor/article-abstract/27/11/5303/3056469?redirectedFrom=fulltext



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Endocannabinoid system; Epileptogenesis; Radial migration; Small GTPases; Subcortical band heterotopia
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Neurosciences
ID Code:46520
Deposited On:22 Feb 2018 11:54
Last Modified:23 Feb 2018 12:17

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