Changes in <scp>CB₁</scp> and <scp>CB₂</scp> receptors in the post‐mortem cerebellum of humans affected by spinocerebellar ataxias

<jats:sec><jats:title>Background and Purpose</jats:title><jats:p>Spinocerebellar ataxias (<jats:styled-content style="fixed-case">SCAs</jats:styled-content>) 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<jats:styled-content style="fixed-case"> SCAs</jats:styled-content> has not been investigated.</jats:p></jats:sec><jats:sec><jats:title>Experimental Approach</jats:title><jats:p>The status of cannabinoid receptor type 1 (<jats:styled-content style="fixed-case">CB<jats:sub>1</jats:sub></jats:styled-content>) and cannabinoid receptor type 2 (<jats:styled-content style="fixed-case">CB<jats:sub>2</jats:sub></jats:styled-content>) receptors in the post‐mortem cerebellum of <jats:styled-content style="fixed-case">SCA</jats:styled-content> patients and controls was investigated using immunohistochemical procedures.</jats:p></jats:sec><jats:sec><jats:title>Key Results</jats:title><jats:p>Immunoreactivity for the <jats:styled-content style="fixed-case">CB<jats:sub>1</jats:sub></jats:styled-content> receptor, and also for the <jats:styled-content style="fixed-case">CB<jats:sub>2</jats:sub></jats:styled-content> receptor, was found in the granular layer, <jats:styled-content style="fixed-case">P</jats:styled-content>urkinje 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 <jats:styled-content style="fixed-case">CB<jats:sub>1</jats:sub></jats:styled-content> and, in particular, <jats:styled-content style="fixed-case">CB<jats:sub>2</jats:sub></jats:styled-content> receptors with calbindin, supporting the presence of these receptors in <jats:styled-content style="fixed-case">P</jats:styled-content>urkinje 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Implications</jats:title><jats:p>Our results demonstrate that <jats:styled-content style="fixed-case">CB<jats:sub>1</jats:sub></jats:styled-content> and <jats:styled-content style="fixed-case">CB<jats:sub>2</jats:sub></jats:styled-content> receptor levels are significantly altered in the cerebellum of <jats:styled-content style="fixed-case">SCA</jats:styled-content> patients. Their identification in <jats:styled-content style="fixed-case">P</jats:styled-content>urkinje neurons, which are the main cells affected in <jats:styled-content style="fixed-case">SCAs</jats:styled-content>, as well as the changes they experienced, suggest that alterations in endocannabinoid receptors may be related to the pathogenesis of <jats:styled-content style="fixed-case">SCAs</jats:styled-content>. Therefore, the endocannabinoid system could provide potential therapeutic targets for the treatment of <jats:styled-content style="fixed-case">SCAs</jats:styled-content> and its progression.</jats:p></jats:sec><jats:sec><jats:title>Linked Articles</jats:title><jats:p>This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1111/bph.2014.171.issue-6">http://dx.doi.org/10.1111/bph.2014.171.issue‐6</jats:ext-link></jats:p></jats:sec>