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

Authors

  • Carmen Rodríguez-Cueto,

    1. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    Search for more papers by this author
  • Cristina Benito,

    1. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, Madrid, Spain
    Search for more papers by this author
  • Javier Fernández-Ruiz,

    Corresponding author
    1. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    • Correspondence

      Javier Fernández-Ruiz and María Gómez-Ruiz, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid 28040, Spain. E-mail: jjfr@med.ucm.es; msgr@med.ucm.es

    Search for more papers by this author
  • Julián Romero,

    1. Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, Madrid, Spain
    Search for more papers by this author
  • Mariluz Hernández-Gálvez,

    1. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    4. Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense, Madrid, Spain
    Search for more papers by this author
  • María Gómez-Ruiz

    Corresponding author
    1. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    4. Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense, Madrid, Spain
    • Correspondence

      Javier Fernández-Ruiz and María Gómez-Ruiz, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid 28040, Spain. E-mail: jjfr@med.ucm.es; msgr@med.ucm.es

    Search for more papers by this author

Abstract

Background and Purpose

Spinocerebellar 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 Approach

The 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 Results

Immunoreactivity 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 Implications

Our 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 Articles

This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6

Ancillary