Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice.
Neurobiol Dis
; 71: 140-50, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-25134728
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 (synaptophysin, vGLUT1 and vGLUT2), of dendritic spine density on MSNs and of MSN sEPSCs, but does not prevent motor impairment. We conclude that loss of excitatory striatal synapses in HD mice is controlled by CB1(MSN) and can be uncoupled from the motor phenotype.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sinapsis
/
Enfermedad de Huntington
/
Cuerpo Estriado
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Receptor Cannabinoide CB1
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Actividad Motora
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Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2014
Tipo del documento:
Article