Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice.

ABSTRACT: Huntington's disease (HD) is caused by an expanded polyglutamine repeat in huntingtin protein that disrupts synaptic function in specific neuronal populations and results in characteristic motor, cognitive and affective deficits. Histopathological hallmarks observed in both HD patients and genetic mouse models include the reduced expression of synaptic proteins, reduced medium spiny neuron (MSN) dendritic spine density and decreased frequency of spontaneous excitatory post-synaptic currents (sEPSCs). Early down-regulation of cannabinoid CB1 receptor expression on MSN (CB1(MSN)) is thought to participate in HD pathogenesis. Here we present a cell-specific genetic rescue of CB1(MSN) in R6/2 mice and report that treatment prevents the reduction of excitatory synaptic markers in the striatum (

SUBMITTER: Naydenov AV 

PROVIDER: S-EPMC4180675 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature