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Metabolomic profiling of three brain regions from a postnatal infected Borna disease virus Hu-H1 rat model

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Abstract

Neonatal rat infection with Borna disease virus (BDV), termed neonatal Borna disease, is an established model for investigating the BDV-associated pathogenesis of neurodevelopmental abnormalities. BDV produces a persistent noncytolytic infection in all culture cell systems assayed to date, while persistent infection in neonatal rats results in a progressive loss of hippocampal granule cells, cerebellar Purkinje cells, and cortical GABA-ergic neurons. Persistent infection also results in behavioral deficits including hyperactivity, cognitive impairment, and abnormal social behavior. However, the molecular mechanisms underlying the neuronal degeneration and behavioral abnormalities remain unclear. Using a metabolomic approach based on gas chromatography coupled with mass spectrometry in conjunction with statistical pattern recognition, the metabolic changes in response to BDV Hu-H1 infection were characterized in the rat hippocampus, cerebellum, and cortex. Metabonomic profiling revealed significant perturbations in nucleotide (e.g., adenosine, uracil, inosine, adenosine-5′-monophosphate, uridine-5′-monophosphate, d-ribose 5-phosphate, and sedoheptulose 7-phosphate), amino acid (e.g., lysine, glycine, phenylalanine, tyrosine, proline, serine, cysteine, aspartic acid, pyroglutamic acid, and γ-aminobutyric acid), lipid (e.g., cholesterol, myristic acid, stearic acid, palmitic acid, 1-monopalmitoylglycerol, and arachidonic acid), and energy (e.g., glucose, lactose, 3-phosphoglyceric acid, and pyruvic acid) metabolites. These metabolites participate in pathways crucial to viral proliferation and neurotransmitter homeostasis. This metabolomic profiling study provides insight into the pathogenic mechanisms of BDV and new directions with which to investigate the in vivo effects of persistent BDV infection.

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Acknowledgments

We thank Professor Hanns Ludwig, AG Bornavirus infections at the Free University of Berlin, Germany, for providing the BDV Hu-H1 strain and antibody in addition to his helpful commentary. We are grateful to Dr. Liv Bode, Robert Koch Institute, Berlin, Germany, for thoroughly reviewing the background virology and proofreading the manuscript. We also thank Dr. N. D. Melgiri for his assistance in editing and proofreading the manuscript. This work was financially supported by the National Basic Research Program of China (973 Program) (Grant No. 2009CB918300), the China Postdoctoral Science Foundation (Grant No. 2012M511911), and the Chongqing Postdoctoral Research Project (Grant No. xm201101003).

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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 of Chongqing Medical University, Chongqing, China

    Yang Lei, Jing Deng, Wei-hua Shao, Song-hua Fan, Hua Huang, Hong-zhi Zhang, Liang Zhang, Wen-juan Li, Rong-zhong Huang, Xia Liu, Chan-juan Zhou & Peng Xie

  2. Institute of Neuroscience, Chongqing Medical University, Chongqing, China

    Yang Lei, Dan Li, Jing Deng, Wei-hua Shao, Song-hua Fan, Xiao Wang, Hua Huang, Shi-gang Chen, Hong-zhi Zhang, Liang Zhang, Yong Zhang, Wen-juan Li, Rong-zhong Huang, Xia Liu, Chan-juan Zhou, Jian-jun Chen & Peng Xie

  3. Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China

    Yang Lei, Dan Li, Jing Deng, Wei-hua Shao, Song-hua Fan, Xiao Wang, Hua Huang, Shi-gang Chen, Hong-zhi Zhang, Liang Zhang, Yong Zhang, Wen-juan Li, Rong-zhong Huang, Xia Liu, Chan-juan Zhou, Jian-jun Chen & Peng Xie

  4. Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing, China

    Dan Li

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Correspondence to Peng Xie.

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Yang Lei and Dan Li contributed equally to this work.

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Lei, Y., Li, D., Deng, J. et al. Metabolomic profiling of three brain regions from a postnatal infected Borna disease virus Hu-H1 rat model. Metabolomics 10, 484–495 (2014). https://doi.org/10.1007/s11306-013-0593-y

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