Differential expression of the neuronal CB1 cannabinoid receptor in the hippocampus of male Ts65Dn Down syndrome mouse model

Nadia Di Franco, Guillaume Drutel, Valérie Roullot-Lacarrière, Francisca Julio-Kalajzic, Valérie Lalanne, Agnès Grel, Thierry Leste-Lasserre, Isabelle Matias, Astrid Cannich, Delphine Gonzales, Vincent Simon, Daniela Cota, Giovanni Marsicano, Pier Vincenzo Piazza, Monique Vallée, Jean-Michel Revest
Molecular and Cellular Neuroscience. 2022-03-01; 119: 103705
DOI: 10.1016/j.mcn.2022.103705

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Down syndrome (DS) or Trisomy 21 is the most common genetic cause of mental retardation with severe learning and memory deficits. DS is due to the complete or partial triplication of human chromosome 21 (HSA21) triggering gene overexpression and protein synthesis alterations responsible for a plethora of mental and physical phenotypes. Among the diverse brain target systems that affect hippocampal-dependent learning and memory deficit impairments in DS, the upregulation of the endocannabinoid system (ECS), and notably the overexpression of the cannabinoid type-1 receptor (CB1), seems to play a major role. Combining various protein and gene expression targeted approaches using western blot, qRT-PCR and FISH techniques, we investigated the expression pattern of ECS components in the hippocampus (HPC) of male Ts65Dn mice. Among all the molecules that constitute the ECS, we found that the expression of the CB1 is altered in the HPC of Ts65Dn mice. CB1 distribution is differentially segregated between the dorsal and ventral part of the HPC and within the different cell populations that compose the HPC. CB1 expression is upregulated in GABAergic neurons of Ts65Dn mice whereas it is downregulated in glutamatergic neurons. These results highlight a complex regulation of the CB1 encoding gene (Cnr1) in Ts65Dn mice that could open new therapeutic solutions for this syndrome.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.


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