Coppi Elisabetta, Cellai Lucrezia, Maraula Giovanna, Dettori Ilaria, Melani Alessia, Pugliese Anna Maria, Pedata Felicita
Department of Health Sciences, University of Florence Florence, Italy.
Department NEUROFARBA, Division of Pharmacology and Toxicology, University of Florence Florence, Italy.
Front Cell Neurosci. 2015 Apr 24;9:155. doi: 10.3389/fncel.2015.00155. eCollection 2015.
Differentiation and maturation of oligodendroglial cells are postnatal processes that involve specific morphological changes correlated with the expression of stage-specific surface antigens and functional voltage-gated ion channels. A small fraction of oligodendrocyte progenitor cells (OPCs) generated during development are maintained in an immature and slowly proliferative or quiescent state in the adult central nervous system (CNS) representing an endogenous reservoir of immature cells. Adenosine receptors are expressed by OPCs and a key role of adenosine in oligodendrocyte maturation has been recently recognized. As evaluated on OPC cultures, adenosine, by stimulating A1 receptors, promotes oligodendrocyte maturation and inhibits their proliferation; on the contrary, by stimulating A2A receptors, it inhibits oligodendrocyte maturation. A1 and A2A receptor-mediated effects are related to opposite modifications of outward delayed rectifying membrane K(+) currents (IK) that are involved in the regulation of oligodendrocyte differentiation. Brain A1 and A2A receptors might represent new molecular targets for drugs useful in demyelinating pathologies, such as multiple sclerosis (MS), stroke and brain trauma.
少突胶质细胞的分化和成熟是出生后的过程,涉及与阶段特异性表面抗原和功能性电压门控离子通道表达相关的特定形态变化。发育过程中产生的一小部分少突胶质前体细胞(OPCs)在成年中枢神经系统(CNS)中维持在未成熟且增殖缓慢或静止的状态,代表未成熟细胞的内源性储备。OPCs表达腺苷受体,最近已认识到腺苷在少突胶质细胞成熟中起关键作用。在OPC培养物上评估时,腺苷通过刺激A1受体促进少突胶质细胞成熟并抑制其增殖;相反,通过刺激A2A受体,它抑制少突胶质细胞成熟。A1和A2A受体介导的效应与外向延迟整流膜K(+)电流(IK)的相反改变有关,IK参与少突胶质细胞分化的调节。脑A1和A2A受体可能代表可用于脱髓鞘疾病(如多发性硬化症(MS)、中风和脑外伤)的药物的新分子靶点。