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. Contrary to other motor disorders, SCAs have not been investigated in relation to the endocannabinoid system.

EXPERIMENTAL APPROACH:

The objective was to investigate the status of CB₁ and CB₂ receptors, using immunohistochemical procedures, in the post-mortem cerebellum of SCA patients and controls.

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 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. In addition, both receptors also co-localized with Iba-1 and GFAP in the granular layer and white matter areas, supporting their additional presence in glial elements, microglia and astrocytes, respectively.

CONCLUSIONS AND IMPLICATIONS:

Our study demonstrates 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 system may be related to the pathogenesis of SCAs, thus supporting that the endocannabinoid system could provide potential therapeutic targets for the treatment of the disease progression in SCAs.
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PMID:

 

23808969

 

[PubMed – as supplied by publisher]