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

Judit Herédi, A. Berkó, Ferenc Jankovics, Tokuko Iwamori, Naoki Iwamori, Etsuro Ono, Szatmár Horváth, Z. Kis, J. Toldi, L. Vécsei, Levente Gellért

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBrain Structure and Function
DOIs
Publication statusAccepted/In press - Aug 27 2016

Fingerprint

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

Keywords

  • Astrocyte
  • Hippocampus
  • Immunohistochemistry
  • In situ hybridization
  • Interneuron
  • Kynurenine aminotransferase-2
  • Mouse
  • Prefrontal cortex
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

Cite this

Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain. / Herédi, Judit; Berkó, A.; Jankovics, Ferenc; Iwamori, Tokuko; Iwamori, Naoki; Ono, Etsuro; Horváth, Szatmár; Kis, Z.; Toldi, J.; Vécsei, L.; Gellért, Levente.

In: Brain Structure and Function, 27.08.2016, p. 1-10.

Research output: Contribution to journalArticle

Herédi, Judit ; Berkó, A. ; Jankovics, Ferenc ; Iwamori, Tokuko ; Iwamori, Naoki ; Ono, Etsuro ; Horváth, Szatmár ; Kis, Z. ; Toldi, J. ; Vécsei, L. ; Gellért, Levente. / Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain. In: Brain Structure and Function. 2016 ; pp. 1-10.
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AU - Iwamori, Naoki

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