Arellano Rogelio O, Sánchez-Gómez María Victoria, Alberdi Elena, Canedo-Antelo Manuel, Chara Juan Carlos, Palomino Aitor, Pérez-Samartín Alberto, Matute Carlos
Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.)
Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
Mol Pharmacol. 2016 Jan;89(1):63-74. doi: 10.1124/mol.115.100594. Epub 2015 Nov 4.
Myelination requires oligodendrocyte-neuron communication, and both neurotransmitters and contact interactions are essential for this process. Oligodendrocytes are endowed with neurotransmitter receptors whose expression levels and properties may change during myelination. However, only scant information is available about the extent and timing of these changes or how they are regulated by oligodendrocyte-neuron interactions. Here, we used electrophysiology to study the expression of ionotropic GABA, glutamate, and ATP receptors in oligodendrocytes derived from the optic nerve and forebrain cultured either alone or in the presence of dorsal root ganglion neurons. We observed that oligodendrocytes from both regions responded to these transmitters at 1 day in culture. After the first day in culture, however, GABA sensitivity diminished drastically to less than 10%, while that of glutamate and ATP remained constant. In contrast, the GABA response amplitude was sustained and remained stable in oligodendrocytes cocultured with dorsal root ganglion neurons. Immunochemistry and pharmacological properties of the responses indicated that they were mediated by distinctive GABAA receptors and that in coculture with neurons, the oligodendrocytes bearing the receptors were those in direct contact with axons. These results reveal that GABAA receptor regulation in oligodendrocytes is driven by axonal cues and that GABA signaling may play a role in myelination and/or during axon-glia recognition.
髓鞘形成需要少突胶质细胞与神经元之间的通讯，神经递质和接触相互作用对这一过程都至关重要。少突胶质细胞具有神经递质受体，其表达水平和特性在髓鞘形成过程中可能会发生变化。然而，关于这些变化的程度和时间，或者它们如何由少突胶质细胞与神经元的相互作用调节，目前只有很少的信息。在这里，我们使用电生理学方法研究了来自视神经和前脑的少突胶质细胞中离子型γ-氨基丁酸（GABA）、谷氨酸和三磷酸腺苷（ATP）受体的表达，这些少突胶质细胞单独培养或在背根神经节神经元存在的情况下培养。我们观察到，来自这两个区域的少突胶质细胞在培养1天时对这些神经递质有反应。然而，在培养的第一天之后，GABA敏感性急剧下降至不到10%，而谷氨酸和ATP的敏感性保持不变。相比之下，在与背根神经节神经元共培养的少突胶质细胞中，GABA反应幅度持续且保持稳定。反应的免疫化学和药理学特性表明，它们是由独特的GABAA受体介导的，并且在与神经元共培养时，携带这些受体的少突胶质细胞是那些与轴突直接接触的细胞。这些结果表明，少突胶质细胞中GABAA受体的调节是由轴突信号驱动的，并且GABA信号可能在髓鞘形成和/或轴突-胶质细胞识别过程中发挥作用。
