Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome.

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome. Neurobiol Dis. 2019 Jan 24;: Authors: Navarro-Romero A, Vázquez-Oliver A, Gomis-González M, Garzón-Montesinos C, Falcón-Moya R, Pastor A, Martín-García E, Pizarro N, Busquets-Garcia A, Revest JM, Piazza PV, Bosch F, Dierssen M, de la Torre R, Rodríguez-Moreno A, Maldonado R, Ozaita A Abstract Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best-characterized preclinical model of Down syndrome, the segmentally trisomic Ts65Dn model. In male Ts65Dn mice, cannabinoid type-1 receptor (CB1R) expression was enhanced and its function increased in hippocampal excitatory terminals. Knockdown of CB1R in the hippocampus of male Ts65Dn mice restored hippocampal-dependent memory. Concomitant with this result, pharmacological inhibition of CB1R restored memory deficits, hippocampal synaptic plasticity and adult neurogenesis in the subgranular zone of the dentate gyrus. Notably...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research