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Author Notes:

Correspondence: Lan Xiao, xiaolan35@hotmail.com; Yue Feng, yfeng@emory.edu

XC, LX, and YF designed the study.

XC, WZ and YG acquired and analyzed the data.

TL, YT and SL also acquired the data.

H-YS analyzed the data.

XC, YF and LX wrote the article, which all other authors reviewed.

All authors approved the final version for publication.

We thank Mrs. Yu Sun for her assistance in ultrathin sections.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

This work is supported by the National Natural Science Foundation of China (NSCF 81471297), and Chongqing Science Foundation to LX.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • oligodendrocyte
  • brain development
  • Olig2 knockout
  • cortical neurons
  • glutamate
  • anxiety behavior
  • MAGNETIC-RESONANCE-SPECTROSCOPY
  • CENTRAL-NERVOUS-SYSTEM
  • NEUROPSYCHIATRIC DISORDERS
  • PSYCHIATRIC-DISORDERS
  • MYELINATION
  • BRAIN
  • DIFFERENTIATION
  • CORTEX
  • NEUROCHEMISTRY
  • IMPULSIVITY

Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice

Tools:

Journal Title:

Frontiers in Cellular Neuroscience

Volume:

Volume 9, Number DEC

Publisher:

, Pages 1-11

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2015 Chen, Zhang, Li, Guo, Tian, Wang, Liu, Shen, Feng and Xiao.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

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