Regulation of glutamate transport in developing rat oligodendrocytes.
Regulation of glutamate transport in developing rat oligodendrocytes.
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DOI：
10.1523/jneurosci.6129-08.2009
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发表时间：
2009-06-17
期刊：
影响因子：
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通讯作者：
Rosenberg PA
中科院分区：
文献类型：
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作者：
DeSilva TM;Kabakov AY;Goldhoff PE;Volpe JJ;Rosenberg PA
从突触囊泡释放的谷氨酸通过刺激谷氨酸受体介导兴奋性神经传递。谷氨酸转运蛋白维持低的突触谷氨酸水平，这对这一过程至关重要，这一作用主要归因于星形胶质细胞。最近，囊泡释放谷氨酸从无髓鞘轴突在大鼠胼胝体已被证明引发AMPA受体介导的电流在神经胶质祖细胞。谷氨酸转运体是谷氨酸清除的唯一机制，然而关于谷氨酸转运体在少突胶质细胞（Oligodendrocytes，OLs）的正常发育或对OLs的兴奋性毒性损伤中的作用知之甚少。我们发现，培养的OL能够钠依赖性摄取谷氨酸，前少突胶质细胞、未成熟OL和成熟OL的Km为10 ± 2 μm，Vmax分别为2.6、5.0和3.8 nmol · min-1 · mg-1。令人惊讶的是，EAAC 1，被认为是唯一的神经元转运蛋白，有助于更多的[3 H] L-谷氨酸摄取的OL比GLT 1或GLAST。这些数据表明，少突胶质细胞上的谷氨酸转运蛋白可能在无髓鞘胼胝体轴突与神经胶质祖细胞进行谷氨酸能信号传导时，在维持谷氨酸稳态方面发挥关键作用。此外，GLT 1显着增加培养的成熟OLs相反，在体内数据中，我们已经表明，虽然GLT 1是存在于发展中的OLs时，无髓鞘轴突在发育中的大鼠胼胝体，髓鞘形成后，GLT 1是不表达的成熟OLs。在大鼠胼胝体中的成熟OL中不存在GLT 1，而在成熟大鼠培养的OL中存在GLT 1，这可能表明体内信号传导过程在体外未被激活。
Glutamate released from synaptic vesicles mediates excitatory neurotransmission by stimulating glutamate receptors. Glutamate transporters maintain low synaptic glutamate levels critical for this process, a role primarily attributed to astrocytes. Recently, vesicular release of glutamate from unmyelinated axons in the rat corpus callosum has been shown to elicit AMPA receptor-mediated currents in glial progenitor cells. Glutamate transporters are the only mechanism of glutamate clearance, yet very little is known about the role of glutamate transporters in normal development of oligodendrocytes (OLs) or in excitotoxic injury to OLs. We found that OLs in culture are capable of sodium-dependent glutamate uptake with a Km of 10 ± 2 μm and a Vmax of 2.6, 5.0, and 3.8 nmol · min−1 · mg−1 for preoligodendrocytes, immature, and mature OLs, respectively. Surprisingly, EAAC1, thought to be exclusively a neuronal transporter, contributes more to [3H]l-glutamate uptake in OLs than GLT1 or GLAST. These data suggest that glutamate transporters on oligodendrocytes may serve a critical role in maintaining glutamate homeostasis at a time when unmyelinated callosal axons are engaging in glutamatergic signaling with glial progenitors. Furthermore, GLT1 was significantly increased in cultured mature OLs contrary to in vivo data in which we have shown that, although GLT1 is present on developing OLs when unmyelinated axons are prevalent in the developing rat corpus callosum, after myelination, GLT1 is not expressed on mature OLs. The absence of GLT1 in mature OLs in the rat corpus callosum and its presence in mature rat cultured OLs may indicate that a signaling process in vivo is not activated in vitro.