Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain.
Brain Struct Funct
; 222(4): 1663-1672, 2017 May.
Article
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| MEDLINE
| ID: mdl-27568378
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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Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Astrocitos
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Transaminasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Brain Struct Funct
Asunto de la revista:
CEREBRO
Año:
2017
Tipo del documento:
Article
País de afiliación:
Hungria