Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice.
Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice.
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少突胶质细胞成熟受损导致幼年小鼠皮质谷氨酸异常增加和焦虑样行为
DOI：
10.3389/fncel.2015.00467
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发表时间：
2015
影响因子：
5.3
通讯作者：
Xiao L
中科院分区：
文献类型：
--
作者：
Chen X;Zhang W;Li T;Guo Y;Tian Y;Wang F;Liu S;Shen HY;Feng Y;Xiao L
青春期是发育适当的少突胶质细胞（OL）-神经元相互作用的关键时期，也是许多认知疾病的发病高峰期，其中焦虑症的患病率最高。然而，是否从头OL发展的障碍导致神经元异常，并有助于在儿童期的焦虑表型的早期发作仍然是未知的。在这项研究中，我们测试了这一假设，即缺陷的OL成熟表明皮质神经元功能，并导致焦虑样行为的幼年小鼠。我们在这里报告，条件性敲除Olig 2基因（Olig 2 cKO），特别是在区分OL在小鼠大脑中优先受损的大脑皮层灰质的OL成熟。有趣的是，局部质子磁共振波谱显示Olig 2 cKO小鼠显示皮质谷氨酸水平异常升高。此外，透射电子显微镜检查显示Olig 2 cKO小鼠皮质中兴奋性突触的囊泡密度增加。此外，幼龄Olig 2 cKO小鼠表现出焦虑样行为和行为抑制受损。综上所述，我们的研究结果表明，受损的OL发展影响大脑皮层中的多巴胺能神经元功能，并导致青少年小鼠的焦虑相关行为。这些发现提出了一个有趣的可能性，即OL缺陷可能是儿童期焦虑发作的一种机制。
Adolescence is the critical time for developing proper oligodendrocyte (OL)-neuron interaction and the peak of onset for many cognitive diseases, among which anxiety disorders display the highest prevalence. However, whether impairment of de novo OL development causes neuronal abnormalities and contributes to the early onset of anxiety phenotype in childhood still remains unexplored. In this study, we tested the hypothesis that defects in OL maturation manifests cortical neuron function and leads to anxiety-like behaviors in juvenile mice. We report here that conditional knockout of the Olig2 gene (Olig2 cKO) specifically in differentiating OLs in the mouse brain preferentially impaired OL maturation in the gray matter of cerebral cortex. Interestingly, localized proton magnetic resonance spectroscopy revealed that Olig2 cKO mice displayed abnormally elevated cortical glutamate levels. In addition, transmission electron microscopy demonstrated increased vesicle density in excitatory glutamatergic synapses in the cortex of the Olig2 cKO mice. Moreover, juvenile Olig2 cKO mice exhibited anxiety-like behaviors and impairment in behavioral inhibition. Taken together, our results suggest that impaired OL development affects glutamatergic neuron function in the cortex and causes anxiety-related behaviors in juvenile mice. These discoveries raise an intriguing possibility that OL defects may be a contributing mechanism for the onset of anxiety in childhood.