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01-05-2017 | Original Article

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

Authors: Judit Herédi, Anikó Magyariné Berkó, Ferenc Jankovics, Tokuko Iwamori, Naoki Iwamori, Etsuro Ono, Szatmár Horváth, Zsolt Kis, József Toldi, László Vécsei, Levente Gellért

Published in: Brain Structure and Function | Issue 4/2017

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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Title: Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain
Authors: Judit Herédi
Anikó Magyariné Berkó
Ferenc Jankovics
Tokuko Iwamori
Naoki Iwamori
Etsuro Ono
Szatmár Horváth
Zsolt Kis
József Toldi
László Vécsei
Levente Gellért
Publication date: 01-05-2017
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 4/2017
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-016-1299-5

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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