Changes in CB1 and CB2 receptors in the post- mortem cerebellum of humans affected by spinocerebellar ataxias

被引:45
作者
Rodriguez-Cueto, Carmen [1 ,2 ,3 ]
Benito, Cristina [1 ,4 ]
Fernandez-Ruiz, Javier [1 ,2 ,3 ]
Romero, Julian [4 ]
Hernandez-Galvez, Mariluz [1 ,2 ,3 ,5 ]
Gomez-Ruiz, Maria [1 ,2 ,3 ,5 ]
机构
[1] Univ Complutense, Fac Med, Dept Bioquim & Biol Mol, Inst Univ Invest Neuroquim, Madrid, Spain
[2] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
[3] Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
[4] Fdn Hosp Alcorcon, Lab Apoyo Invest, Madrid, Spain
[5] Univ Complutense, Fac Psicol, Dept Psicobiol, E-28040 Madrid, Spain
关键词
cannabinoids; endocannabinoid system; CB1 and CB2 receptors; cerebellum; Purkinje neurons; spinocerebellar ataxias; ACID AMIDE HYDROLASE; ENDOGENOUS CANNABINOID SYSTEM; HUNTINGTONS-DISEASE; ENDOCANNABINOID SYSTEM; MULTIPLE-SCLEROSIS; SPINAL-CORD; PARKINSONS-DISEASE; BRAIN; EXPRESSION; TARGET;
D O I
10.1111/bph.12283
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and PurposeSpinocerebellar ataxias (SCAs) are a family of chronic progressive neurodegenerative diseases, clinically and genetically heterogeneous, characterized by loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. Unlike other motor disorders, the possible role of changes in the endocannabinoid system in the pathogenesis of SCAs has not been investigated. Experimental ApproachThe status of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) receptors in the post-mortem cerebellum of SCA patients and controls was investigated using immunohistochemical procedures. Key ResultsImmunoreactivity for the CB1 receptor, and also for the CB2 receptor, was found in the granular layer, Purkinje cells, neurons of the dentate nucleus and areas of white matter in the cerebellum of SCA patients at levels notably higher than controls. Double-labelling procedures demonstrated co-localization of CB1 and, in particular, CB2 receptors with calbindin, supporting the presence of these receptors in Purkinje neurons. Both receptors also co-localized with Iba-1 and glial fibrillary acidic protein in the granular layer and white matter areas, indicating that they are present in microglia and astrocytes respectively. Conclusions and ImplicationsOur results demonstrate that CB1 and CB2 receptor levels are significantly altered in the cerebellum of SCA patients. Their identification in Purkinje neurons, which are the main cells affected in SCAs, as well as the changes they experienced, suggest that alterations in endocannabinoid receptors may be related to the pathogenesis of SCAs. Therefore, the endocannabinoid system could provide potential therapeutic targets for the treatment of SCAs and its progression. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit
引用
收藏
页码:1472 / 1489
页数:18
相关论文
共 50 条
[31]   Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas [J].
Lopez De Jesus, Maider ;
Hostalot, Cristina ;
Garibi, Jesus M. ;
Salles, Joan ;
Javier Meana, J. ;
Callado, Luis F. .
NEUROCHEMISTRY INTERNATIONAL, 2010, 56 (6-7) :829-833
[32]   Heteromers Formed by GPR55 and Either Cannabinoid CB1 or CB2 Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients [J].
Menendez-Perez, Carlota ;
Rivas-Santisteban, Rafael ;
del Valle, Eva ;
Tolivia, Jorge ;
Navarro, Ana ;
Franco, Rafael ;
Martinez-Pinilla, Eva .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (08)
[33]   Genetic deletion of the cannabinoid receptors CB1 and CB2 enhances inflammation with diverging effects on skin wound healing in mice [J].
Ruhl, Tim ;
Lippold, Ella F. ;
Christer, Tim ;
Schaefer, Benedikt ;
Kim, Bong-Sung ;
Beier, Justus P. .
LIFE SCIENCES, 2021, 285
[34]   Spinal cannabinoid CB1 or CB2 receptors activation attenuates mechanical allodynia in streptozotocin-induced diabetic rats [J].
Goncalves, Maryna Rodrigues ;
da Conceicao, Milena Santana ;
Alves Jesus, Carlos Henrique ;
Gasparin, Alexia Thamara ;
Rosa, Evelize Stacoviaki ;
da Cunha, Joice Maria .
BEHAVIOURAL PHARMACOLOGY, 2022, 33 (2-3) :158-164
[35]   Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: changes following experimental parkinsonism [J].
Sierra, Salvador ;
Luquin, Natasha ;
Rico, Alberto J. ;
Gomez-Bautista, Virginia ;
Roda, Elvira ;
Dopeso-Reyes, Iria G. ;
Vazquez, Alfonso ;
Martinez-Pinilla, Eva ;
Labandeira-Garcia, Jose L. ;
Franco, Rafael ;
Lanciego, Jose L. .
BRAIN STRUCTURE & FUNCTION, 2015, 220 (05) :2721-2738
[36]   Cannabinoids in pain management: CB1, CB2 and non-classic receptor ligands [J].
Davis, Mellar P. .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2014, 23 (08) :1123-1140
[37]   Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat [J].
Elmes, SJR ;
Winyard, LA ;
Medhurst, SJ ;
Clayton, NM ;
Wilson, AW ;
Kendall, DA ;
Chapman, V .
PAIN, 2005, 118 (03) :327-335
[38]   The hypothermic response to bacterial lipopolysaccharide critically depends on brain CB1, but not CB2 or TRPV1, receptors [J].
Steiner, Alexandre A. ;
Molchanova, Alla Y. ;
Dogan, M. Devrim ;
Patel, Shreya ;
Petervari, Erika ;
Balasko, Marta ;
Wanner, Samuel P. ;
Eales, Justin ;
Oliveira, Daniela L. ;
Gavva, Narender R. ;
Almeida, M. Camila ;
Szekely, Miklos ;
Romanovsky, Andrej A. .
JOURNAL OF PHYSIOLOGY-LONDON, 2011, 589 (09) :2415-2431
[39]   Targeting endocannabinoid degradation protects against experimental colitis in mice:: involvement of CB1 and CB2 receptors [J].
Storr, Martin A. ;
Keenan, Catherine M. ;
Emmerdinger, Dominik ;
Zhang, Hong ;
Yuece, Birol ;
Sibaev, Andrei ;
Massa, Federico ;
Buckley, Nancy E. ;
Lutz, Beat ;
Goeke, Burkhard ;
Brand, Stephan ;
Patel, Kamala D. ;
Sharkey, Keith A. .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2008, 86 (08) :925-936
[40]   Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract [J].
Galiazzo, Giorgia ;
Giancola, Fiorella ;
Stanzani, Agnese ;
Fracassi, Federico ;
Bernardini, Chiara ;
Forni, Monica ;
Pietra, Marco ;
Chiocchetti, Roberto .
HISTOCHEMISTRY AND CELL BIOLOGY, 2018, 150 (02) :187-205