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Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain

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Abstract

During catabolism of tryptophan through the kynurenine (KYN) pathway, several endogenous metabolites with neuromodulatory properties are produced, of which kynurenic acid (KYNA) is one of the highest significance. The causal role of altered KYNA production has been described in several neurodegenerative and neuropsychiatric disorders (e.g., Parkinson’s disease, Huntington’s disease, schizophrenia) and therefore kynurenergic manipulation with the aim of therapy has recently been proposed. Conventionally, KYNA is produced from its precursor l-KYN with the aid of the astrocytic kynurenine aminotransferase-2 (KAT-2) in the murine brain. Although the mouse is a standard therapeutic research organism, the presence of KAT-2 in mice has not been described in detail. This study demonstrates the presence of kat-2 mRNA and protein throughout the adult C57Bl6 mouse brain. In addition to the former expression data from the rat, we found prominent KAT-2 expression not only in the astrocyte, but also in neurons in several brain regions (e.g., hippocampus, substantia nigra, striatum, and prefrontal cortex). A significant number of the KAT-2 positive neurons were positive for GAD67; the presence of the KAT-2 enzyme we could also demonstrate in mice brain homogenate and in cells overexpressing recombinant mouse KAT-2 protein. This new finding attributes a new role to interneuron-derived KYNA in neuronal network operation. Furthermore, our results suggest that the thorough investigation of the spatio-temporal expression pattern of the relevant enzymes of the KYN pathway is a prerequisite for developing and understanding the pharmacological and transgenic murine models of kynurenergic manipulation.

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Acknowledgments

This study was supported by grant OTKA K105077 and co-financed by the EUROHEADPAIN FP7-Health 2013-Innovation; Grant No. 602633, and Grant by MTA-SZTE Neuroscience Research Group. LG was a fellow in the JSPS Fellowship Programs for Overseas Researchers PE15040. Thanks are due to Dr. Mónika Kiricsi for her assistance to membrane scanning at the Department of Biochemistry and Molecular Biology, SZTE. Thanks are due to Matthew Higginson for grammar proofreading.

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Authors and Affiliations

  1. Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary

    Judit Herédi, Anikó Magyariné Berkó, Zsolt Kis, József Toldi & Levente Gellért

  2. Biological Research Center of the Hungarian Academy of Sciences, Temesvári ave. 62, Szeged, 6726, Hungary

    Ferenc Jankovics

  3. Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Tokuko Iwamori, Naoki Iwamori & Etsuro Ono

  4. Department of Physiological Sciences, Graduate School of Medical Sciences, Center of Biomedical Research, Research Center for Human Disease Modeling, Kyushu University, Fukuoka, 812-8582, Japan

    Tokuko Iwamori, Naoki Iwamori & Etsuro Ono

  5. Department of Neurology, Faculty of Medicine, University of Szeged, Semmelweis st.6, Szeged, 6725, Hungary

    László Vécsei

  6. MTA-SZTE Neuroscience Research Group, University of Szeged, Semmelweis st.6, Szeged, 6725, Hungary

    József Toldi, László Vécsei & Levente Gellért

  7. Department of Psychiatry, Vanderbilt University, Nashville, TN, 37232, USA

    Szatmár Horváth

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  1. Judit Herédi
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Correspondence to Levente Gellért.

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Herédi, J., Berkó, A.M., Jankovics, F. et al. Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain. Brain Struct Funct 222, 1663–1672 (2017). https://doi.org/10.1007/s00429-016-1299-5

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