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Metabolomic identification of molecular changes associated with stress resilience in the chronic mild stress rat model of depression

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Abstract

Chronic stressful events are key risk factors for major depressive disorder (MDD), yet some individuals exposed to stressful events do not develop MDD. This disparity suggests the significance of resilience to deleterious stress effects. However, the underlying molecular mechanisms of stress resilience are poorly understood. In the present study, the chronic mild stress (CMS) rat model of depression was used to reveal the individual differences in stress response. Employing a gas chromatography/mass spectrometry metabolomic approach, the molecular changes associated with stress resilience in rat cerebellum were characterized by comparing anhedonic, CMS resilient and control groups. The results showed that four cerebellar metabolites—proline, lysine, glutamine, and dihydroxyacetone phosphate—were identified as the key differential metabolites associated with stress resilience. These metabolites may play a potential role in rendering individuals less vulnerable to CMS exposure. These findings provide insight into the molecular mechanisms underlying stress resilience and shed light on novel therapeutic opportunities to augment stress resiliency.

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Acknowledgments

This work was financially supported by the National Basic Research Program of China (973 Program, Grant No. 2009CB918300). This manuscript was edited and proofread by Dr. N. D. Melgiri.

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The authors have declared no conflict of interest in the submission of this manuscript.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Wei-Hua Shao, Song-Hua Fan, Yang Lei, Guo-En Yao, Hong-Bo Xu, Hai-Peng Liu, Peng Zheng & Peng Xie

  2. Chongqing Key Laboratory of Neurobiology, Chongqing, People’s Republic of China

    Wei-Hua Shao, Song-Hua Fan, Yang Lei, Guo-En Yao, Jian-Jun Chen, Jian Zhou, Hong-Bo Xu, Hai-Peng Liu, Bo Wu, Peng Zheng, Liang Fang & Peng Xie

  3. Institute of Neuroscience, Chongqing Medical University, Chongqing, People’s Republic of China

    Wei-Hua Shao, Song-Hua Fan, Yang Lei, Guo-En Yao, Jian-Jun Chen, Jian Zhou, Hong-Bo Xu, Hai-Peng Liu, Bo Wu, Peng Zheng, Liang Fang & Peng Xie

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  1. Wei-Hua Shao
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  2. Song-Hua Fan
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  12. Peng Xie
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Correspondence to Peng Xie.

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Wei-Hua Shao, Song-Hua Fan, Yang Lei, and Guo-En Yao contributed equally to this work.

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Shao, WH., Fan, SH., Lei, Y. et al. Metabolomic identification of molecular changes associated with stress resilience in the chronic mild stress rat model of depression. Metabolomics 9, 433–443 (2013). https://doi.org/10.1007/s11306-012-0460-2

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