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Chronic treatment with anti-bipolar drugs suppresses glutamate release from astroglial cultures

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Abstract

Astroglial cells are fundamental elements of most neurological diseases, including bipolar disorders in which astrocytes show morphological and functional deficiency. Here we report the suppression of astroglial glutamate release by chronic treatment with three anti-bipolar drugs, lithium salt (Li+), carbamazepine (CBZ) and valproic acid (VPA). Release of glutamate was triggered by transient exposure of astrocytes to ATP (which activated purinoceptors) and 45 mM K+ (which depolarised cell membrane to ~−30 mV). In both types of stimulation glutamate release was regulated by Ca2+ entry through plasmalemmal channels and by Ca2+ release from the endoplasmic reticulum (ER) intracellular stores. Exposure of astroglial cultures to Li+, CBZ and VPA for 2 weeks led to a significant (more than 2 times) inhibition of glutamate release, which may alleviate the hyperactivity of the glutamatergic transmission in the brain of patients with bipolar disorders and thus contribute the underlying mechanism of drug action.

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Acknowledgments

This study was supported by Grant No. 31440048 from the National Natural Science Foundation of China. AV was supported in part by the grant (agreement from August 27 2013 No. 02.B.49.21.0003) between The Ministry of Education and Science of the Russian Federation and Lobachevsky State University of Nizhny Novgorod and by the grant of the Russian Scientific Foundation №14-15-00633.

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The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, People’s Republic of China

      Zhuo Liu, Dan Song, Enzhi Yan & Liang Peng

    2. Faculty of Life Science, The University of Manchester, Manchester, UK

      Alexei Verkhratsky

    3. Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

      Alexei Verkhratsky

    4. University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia

      Alexei Verkhratsky

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    1. Zhuo Liu
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    2. Dan Song
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    3. Enzhi Yan
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    4. Alexei Verkhratsky
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    5. Liang Peng
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    Correspondence to Liang Peng.

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    Handling Editor: N. Singewald.

    Z. Liu and D. Song contributed equally to this article.

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    Liu, Z., Song, D., Yan, E. et al. Chronic treatment with anti-bipolar drugs suppresses glutamate release from astroglial cultures. Amino Acids 47, 1045–1051 (2015). https://doi.org/10.1007/s00726-015-1936-y

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