Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.
Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.
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DOI：
10.1038/srep23084
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发表时间：
2016-03-15
影响因子：
4.6
通讯作者：
Tohyama M
中科院分区：
文献类型：
--
作者：
Miyata S;Taniguchi M;Koyama Y;Shimizu S;Tanaka T;Yasuno F;Yamamoto A;Iida H;Kudo T;Katayama T;Tohyama M
反复的压力事件与重性抑郁症（MDD）的发作有关。我们以前显示少突胶质细胞（OL）特异性激活的血清/糖皮质激素调节激酶（SGK）1级联反应，轴突髓鞘粘附分子的表达增加，和制定的少突胶质细胞乔木在胼胝体的慢性应激小鼠。在目前的研究中，我们证明，在胼胝体的朗维尔节点和paranodes在这些小鼠较窄。慢性应激还导致Caspr和Kv 1.1的弥漫性重新分布，并降低了白色物质中的活性，表明OL的形态学变化与轴突活性抑制之间存在联系。OL原代培养物进行慢性应激导致SGK 1激活和易位到细胞核，在那里它抑制代谢型谷氨酸受体（mGluRs）的转录。此外，慢性应激暴露降低了OLs的cAMP水平和膜电位。我们通过扩散张量成像显示，MDD患者的胼胝体表现出各向异性分数降低，反映了可能由轴突损伤引起的白色物质完整性受损。我们的研究结果表明，慢性应激通过抑制mGluR在OLs中的激活来破坏朗维尔结的组织，并且特定的白色物质异常与MDD发作密切相关。
Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset.