title: Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain.
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.
authors: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary.
authors: Judit
authors: J
authors: Herédi
authors: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary.
authors: Anikó Magyariné
authors: AM
authors: Berkó
authors: Biological Research Center of the Hungarian Academy of Sciences, Temesvári ave. 62, Szeged, 6726, Hungary.
authors: Ferenc
authors: F
authors: Jankovics
authors: Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.|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.
authors: Tokuko
authors: T
authors: Iwamori
authors: Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.|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.
authors: Naoki
authors: N
authors: Iwamori
authors: Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.|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.
authors: Etsuro
authors: E
authors: Ono
authors: Department of Psychiatry, Vanderbilt University, Nashville, TN, 37232, USA.
authors: Szatmár
authors: S
authors: Horváth
authors: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary.
authors: Zsolt
authors: Z
authors: Kis
authors: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary.|MTA-SZTE Neuroscience Research Group, University of Szeged, Semmelweis st.6, Szeged, 6725, Hungary.
authors: József
authors: J
authors: Toldi
authors: Department of Neurology, Faculty of Medicine, University of Szeged, Semmelweis st.6, Szeged, 6725, Hungary.|MTA-SZTE Neuroscience Research Group, University of Szeged, Semmelweis st.6, Szeged, 6725, Hungary.
authors: László
authors: L
authors: Vécsei
authors: Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary. gellert.levente1@gmail.com.|MTA-SZTE Neuroscience Research Group, University of Szeged, Semmelweis st.6, Szeged, 6725, Hungary. gellert.levente1@gmail.com.
authors: Levente
authors: http://orcid.org/0000-0003-2254-2970
authors: L
authors: Gellért
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D000637:Transaminases / Q000032:analysis*
chemical_list: D012333:RNA, Messenger; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase
keywords: Astrocyte; Hippocampus; Immunohistochemistry; In situ hybridization; Interneuron; Kynurenine aminotransferase-2; Mouse; Prefrontal cortex; Striatum; Substantia nigra