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Decreased Astroglial Monocarboxylate Transporter 4 Expression in Temporal Lobe Epilepsy

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Abstract

Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under conditions of increased demand. Disruption of this astroglial-neuron metabolic coupling pathway may contribute to epileptogenesis. We measured MCT4 expression in temporal lobe epileptic foci excised from patients with intractable epilepsy and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients compared with controls, due at least partially to MCT4 promoter methylation. Expression of MCT4 also decreased progressively in pilocarpine-treated rats from 12 h to 14 days post-administration. Underexpression of MCT4 in cultured astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1) expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate.

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Acknowledgments

The authors sincerely thank the patients and their families for their participation in this study. This work was supported by grants from the National Natural Science Foundation of China (no. 81271433). Funding organizations had no influence on the contents or on any other aspect of the article.

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China

    Bei Liu, Chao Wang, Jie Li, Ye Tao, Qiang Meng, Qian-Li Yang, Guo-Dong Gao & Hua Zhang

  2. Department of Anatomy, School of Basic Medical Sciences, The Fourth Military Medical University, Xi’an, People’s Republic of China

    Le Niu

  3. Department of Cardiology, Hainan Branch of PLA General Hospital, Sanya, People’s Republic of China

    Ming-Zhi Shen

  4. Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China

    Lei Gao

  5. Department of Neurological Rehabilitation, Children’s Hospital of Zhengzhou City, Zhengzhou, People’s Republic of China

    Li-Jia Song

  6. Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xin-shi Road, Xi’an, 710038, People’s Republic of China

    Guo-Dong Gao & Hua Zhang

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  1. Bei Liu
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Correspondence to Guo-Dong Gao or Hua Zhang.

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Bei Liu, Le Niu, Ming-Zhi Shen, and Lei Gao contributed equally to this work.

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Liu, B., Niu, L., Shen, MZ. et al. Decreased Astroglial Monocarboxylate Transporter 4 Expression in Temporal Lobe Epilepsy. Mol Neurobiol 50, 327–338 (2014). https://doi.org/10.1007/s12035-013-8619-z

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