脊髓小脑共济失调患者死后小脑 CB(1)和 CB(2)受体的变化。
Changes in CB(1) and CB(2) receptors in the post-mortem cerebellum of humans affected by spinocerebellar ataxias.
机构信息
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
出版信息
Br J Pharmacol. 2014 Mar;171(6):1472-89. doi: 10.1111/bph.12283.
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.
背景与目的
脊髓小脑共济失调（SCA）是一组慢性进行性神经退行性疾病，具有临床和遗传异质性，其特征是由于小脑及其传入和传出连接的退化导致平衡和运动协调丧失。与其他运动障碍不同，内源性大麻素系统在 SCA 发病机制中的可能作用尚未得到研究。
实验方法
使用免疫组织化学程序研究 SCA 患者和对照组死后小脑中海马受体 1（CB1）和海马受体 2（CB2）受体的状态。
主要结果
在 SCA 患者的小脑颗粒层、浦肯野细胞、齿状核神经元和白质区域中，CB1 受体和 CB2 受体的免疫反应性明显高于对照组。双标记程序表明 CB1 受体，特别是 CB2 受体与钙结合蛋白共定位，支持这些受体存在于浦肯野神经元中。两种受体在颗粒层和白质区域也与 Iba-1 和胶质纤维酸性蛋白共定位，表明它们分别存在于小胶质细胞和星形胶质细胞中。
结论和意义
我们的结果表明，CB1 和 CB2 受体水平在 SCA 患者的小脑中有显著改变。它们在浦肯野神经元中的鉴定（浦肯野神经元是 SCA 中受影响的主要细胞）以及它们经历的变化表明，内源性大麻素受体的改变可能与 SCA 的发病机制有关。因此，内源性大麻素系统可能为治疗 SCA 及其进展提供潜在的治疗靶点。
相关文章
本文是 2013 年大麻素专题的一部分。要查看该部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2014.171.issue-6.
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