Worsening of Huntington disease phenotype in CB1 receptor knockout mice.Neurobiol Dis. 2011 Jun; 42(3):524-9.ND
Huntington's disease (HD) is a progressive neurodegenerative genetic disorder which leads to motor, cognitive and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. Cannabinoid CB1 receptors (CB1Rs) are particularly enriched in the striatum and previous works indicate their early loss of expression in HD, even before symptom occurrence. However, pathophysiological significance of this loss of expression remains unclear. In addition, whether specific modulation of CB1R is able to mitigate striatal neuron fate in HD remains currently controversial. In order to gain further insights on the potential role of CB1R in HD physiopathology, we evaluated the pathophysiological consequences of a genetic deletion of CB1R in the N171-82Q transgenic model and following 3-nitropropionic (3NP) intoxication. Taken together our data demonstrate that CB1R knockout (1) worsens motor performances in N171-82Q mice and (2) increases mouse susceptibility to 3NP. These results suggest that functional changes in CB1R may contribute to the physiopathological development of HD.