Cannabinoid CB1 receptors are early downregulated followed by a further upregulation in the basal ganglia of mice with deletion of specific park genes.
J Neural Transm Suppl
; (73): 269-75, 2009.
Article
en En
| MEDLINE
| ID: mdl-20411785
ABSTRACT
This study was designed to examine the type of changes experienced by the CB1 receptor, a key element of the cannabinoid signaling system, in the basal ganglia of different mouse mutants generated by deletion of specific genes associated with the development of Parkinson's disease in humans [PARK1 (alpha-synuclein), PARK2 (parkin) or PARK6 (PINK1)]. We observed that CB1 receptor-mRNA levels were significantly reduced in the caudate-putamen in the three models under examination when animals were analyzed at early phases (< or = 12 months of age). This decrease was, in general, associated with a reduction in CB1 receptor binding in the substantia nigra and the globus pallidus, particularly in the case of alpha-synuclein-deficient mice. By contrast, both parameters, mRNA levels and binding for the CB1 receptor, showed an elevation in the same areas when animals were analyzed at older ages, mainly in the case of the CB1 receptor binding in the substantia nigra. In summary, our data revealed the existence of a biphasic response for CB1 receptors, with losses at early phases, when dopaminergic dysfunction is possibly the major event that takes place, followed by upregulatory responses at advanced phases characterized by the occurrence of evident nigrostriatal pathology including neuronal death in some cases.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ganglios Basales
/
Regulación hacia Abajo
/
Regulación hacia Arriba
/
Ubiquitina-Proteína Ligasas
/
Receptor Cannabinoide CB1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neural Transm Suppl
Año:
2009
Tipo del documento:
Article
País de afiliación:
España