title: Cannabinoid CB1 receptors are early downregulated followed by a further upregulation in the basal ganglia of mice with deletion of specific park genes.
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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Moisés
authors.initials: M
authors.lastname: García-Arencibia
authors.forename: Concepción
authors.initials: C
authors.lastname: García
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez-Navarro
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert-Sáchez
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mena
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Justo García
authors.initials: JG
authors.lastname: de Yébenes
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
mesh_terms: D000367:Age Factors; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001479:Basal Ganglia / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000145:classification / Q000172:deficiency*; D015854:Up-Regulation / Q000235:genetics*; D051844:alpha-Synuclein / Q000172:deficiency
chemical_list: D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein