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

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

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)1663-1672
ページ数10
ジャーナルBrain Structure and Function
222
発行部数4
DOI
出版物ステータス出版済み - 5 1 2017

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kynurenine-oxoglutarate transaminase
Kynurenic Acid
Kynurenine
Brain
Therapeutic Human Experimentation
Neurons
Huntington Disease
Interneurons
Substantia Nigra
Enzymes
Prefrontal Cortex
Tryptophan
Astrocytes
Neurodegenerative Diseases
Parkinson Disease
Hippocampus
Schizophrenia
Proteins
Pharmacology

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Neuroscience(all)
  • Histology

これを引用

Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain. / Herédi, Judit; Berkó, Anikó Magyariné; Jankovics, Ferenc; Iwamori, Tokuko; Iwamori, Naoki; Ono, Etsuro; Horváth, Szatmár; Kis, Zsolt; Toldi, József; Vécsei, László; Gellért, Levente.

:: Brain Structure and Function, 巻 222, 番号 4, 01.05.2017, p. 1663-1672.

研究成果: ジャーナルへの寄稿記事

Herédi, J, Berkó, AM, Jankovics, F, Iwamori, T, Iwamori, N, Ono, E, Horváth, S, Kis, Z, Toldi, J, Vécsei, L & Gellért, L 2017, 'Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain', Brain Structure and Function, 巻. 222, 番号 4, pp. 1663-1672. https://doi.org/10.1007/s00429-016-1299-5
Herédi, Judit ; Berkó, Anikó Magyariné ; Jankovics, Ferenc ; Iwamori, Tokuko ; Iwamori, Naoki ; Ono, Etsuro ; Horváth, Szatmár ; Kis, Zsolt ; Toldi, József ; Vécsei, László ; Gellért, Levente. / Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain. :: Brain Structure and Function. 2017 ; 巻 222, 番号 4. pp. 1663-1672.
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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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AU - Herédi, Judit

AU - Berkó, Anikó Magyariné

AU - Jankovics, Ferenc

AU - Iwamori, Tokuko

AU - Iwamori, Naoki

AU - Ono, Etsuro

AU - Horváth, Szatmár

AU - Kis, Zsolt

AU - Toldi, József

AU - Vécsei, László

AU - Gellért, Levente

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N2 - 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.

AB - 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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