Arévalo-Martín Angel, García-Ovejero Daniel, Rubio-Araiz Ana, Gómez Oscar, Molina-Holgado Francisco, Molina-Holgado Eduardo
Laboratorio de Neuroinflamación, Unidad de Neurología Experimental (associated to the Instituto Cajal, CSIC, Madrid, Spain), Hospital Nacional de Parapléjicos, SESCAM, 45071 Toledo, Spain.
Eur J Neurosci. 2007 Sep;26(6):1548-59. doi: 10.1111/j.1460-9568.2007.05782.x.
The subventricular zone (SVZ) is a source of post-natal glial precursors that can migrate to the overlying white matter, where they may differentiate into oligodendrocytes. We showed that, in the post-natal SVZ ependymocytes, radial glia and astrocyte-like cells express cannabinoid receptor 1 (CB1), whereas cannabinoid receptor 2 (CB2) is found in cells expressing the polysialylated neural cell adhesion molecule. To study CB1 and CB2 function, post-natal rats were exposed to selective CB1 or CB2 agonists (arachidonyl-2-chloroethylamide and JWH-056, respectively) for 15 days. Accordingly, we found that CB1 activation increases the number of Olig2-positive cells in the dorsolateral SVZ, whereas CB2 activation increases polysialylated neural cell adhesion molecule expression in this region. As intense myelination occurs during the first weeks of post-natal development, we examined how modulating these factors affected the expression of myelin basic protein. Pharmacological administration of agonists and antagonists of CB1 and CB2 showed that the activation of both receptors is needed to augment the expression of myelin basic protein in the subcortical white matter.
脑室下区(SVZ)是出生后神经胶质前体细胞的来源,这些细胞可迁移至上覆的白质,在那里它们可能分化为少突胶质细胞。我们发现,在出生后的SVZ室管膜细胞、放射状胶质细胞和星形胶质样细胞中表达大麻素受体1(CB1),而在表达多唾液酸神经细胞黏附分子的细胞中发现大麻素受体2(CB2)。为了研究CB1和CB2的功能,将出生后的大鼠分别暴露于选择性CB1或CB2激动剂(分别为花生四烯酸-2-氯乙酰胺和JWH-056)15天。相应地,我们发现CB1激活增加了背外侧SVZ中Olig2阳性细胞的数量,而CB2激活增加了该区域多唾液酸神经细胞黏附分子的表达。由于在出生后发育的最初几周会发生强烈的髓鞘形成,我们研究了调节这些因子如何影响髓鞘碱性蛋白的表达。对CB1和CB2的激动剂和拮抗剂进行药理学给药表明,需要激活这两种受体才能增加皮质下白质中髓鞘碱性蛋白的表达。