Deletion of the Sodium-Dependent Glutamate Transporter GLT-1 in Maturing Oligodendrocytes Attenuates Myelination of Callosal Axons During a Postnatal Phase of Central Nervous System Development.
Deletion of the Sodium-Dependent Glutamate Transporter GLT-1 in Maturing Oligodendrocytes Attenuates Myelination of Callosal Axons During a Postnatal Phase of Central Nervous System Development.
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DOI：
10.3389/fncel.2022.905299
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发表时间：
2022
影响因子：
5.3
通讯作者：
Fuss, Babette
中科院分区：
文献类型：
--
作者：
Thomason, Elizabeth J.;Suarez-Pozos, Edna;Afshari, Fatemah S.;Rosenberg, Paul A.;Dupree, Jeffrey L.;Fuss, Babette
钠依赖性谷氨酸转运蛋白GLT-1（EAAT 2，SLC 1A 2）已被充分描述为中枢神经系统（CNS）中细胞外谷氨酸稳态的重要调节剂，该功能主要通过其在星形胶质细胞上的存在来执行。然而，越来越多的证据表明GLT-1在CNS细胞而不是星形胶质细胞中表达，并且在谷氨酸摄取下游机制介导的功能作用中表达。在这种情况下，据报道GLT-1在神经元和少突胶质细胞（OLG）中都有表达，并且GLT-1在神经元突触前的存在与谷氨酸摄取、基因表达和线粒体功能的调节有关。目前对OLG表达的GLT-1的功能作用知之甚少。这里提供的数据提供了第一个证据表明，成熟OLG表达的GLT-1有助于调节CNS中的发育髓鞘形成。更具体地说，使用诱导型和条件性敲除小鼠，其中GLT-1在成熟OLG中在髓鞘形成的高峰期（2至4周龄之间）被删除，揭示了优先雄性小鼠胼胝体中的髓鞘形成不足的特征。这些特征包括较小直径的有髓轴突的百分比降低和髓鞘厚度降低。有趣的是，没有发现这种髓鞘形成表型与髓鞘基因表达的主要变化相关。总之，这里提供的数据表明，GLT-1成熟OLG表达的参与调制的形态学方面与CNS髓鞘形成在至少胼胝体和在一个发展窗口，男性相比，女性显得特别脆弱。
The sodium-dependent glutamate transporter GLT-1 (EAAT2, SLC1A2) has been well-described as an important regulator of extracellular glutamate homeostasis in the central nervous system (CNS), a function that is performed mainly through its presence on astrocytes. There is, however, increasing evidence for the expression of GLT-1 in CNS cells other than astrocytes and in functional roles that are mediated by mechanisms downstream of glutamate uptake. In this context, GLT-1 expression has been reported for both neurons and oligodendrocytes (OLGs), and neuronal presynaptic presence of GLT-1 has been implicated in the regulation of glutamate uptake, gene expression, and mitochondrial function. Much less is currently known about the functional roles of GLT-1 expressed by OLGs. The data presented here provide first evidence that GLT-1 expressed by maturing OLGs contributes to the modulation of developmental myelination in the CNS. More specifically, using inducible and conditional knockout mice in which GLT-1 was deleted in maturing OLGs during a peak period of myelination (between 2 and 4 weeks of age) revealed hypomyelinated characteristics in the corpus callosum of preferentially male mice. These characteristics included reduced percentages of smaller diameter myelinated axons and reduced myelin thickness. Interestingly, this myelination phenotype was not found to be associated with major changes in myelin gene expression. Taken together, the data presented here demonstrate that GLT-1 expressed by maturing OLGs is involved in the modulation of the morphological aspects associated with CNS myelination in at least the corpus callosum and during a developmental window that appears of particular vulnerability in males compared to females.
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DOI：
10.1523/jneurosci.6129-08.2009
发表时间：
2009-06-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
DeSilva TM;Kabakov AY;Goldhoff PE;Volpe JJ;Rosenberg PA
通讯作者：
Rosenberg PA
影响因子：
2.5
作者：
CALEY, DW;MAXWELL, DS
通讯作者：
MAXWELL, DS
影响因子：
7.8
作者：
Dupree, J L;Girault, J A;Popko, B
通讯作者：
Popko, B
影响因子：
25
作者：
Baraban M;Koudelka S;Lyons DA
通讯作者：
Lyons DA
DOI：
10.1038/ejhg.2014.261
发表时间：
2015-09
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
通讯作者：
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