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Ammonia upregulates kynurenine aminotransferase II mRNA expression in rat brain: a role for astrocytic NMDA receptors?

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Abstract

Kynurenine aminotransferase II (KAT-II) is the astrocytic enzyme catalyzing the synthesis of kynurenic acid (KYNA), an endogenous inhibitor of the α7-nicotinic receptor and the NMDA receptor (NMDAr). A previous study demonstrated an increase of KYNA synthesis in the brain of rats with thioacetamide (TAA)-induced acute liver failure. Here we show that TAA administration increases KAT-II expression in the rat cerebral cortex and the effect is mimicked in cerebral cortical astrocytes in culture treated with high (5 mM) concentration of ammonia. KAT-II expression in control and TAA-treated rats was increased by NMDAr antagonist memantine, and the effects of TAA and memantine appeared additive. In astrocytes, the NMDAr antagonist MK-801 raised KAT-II expression as well, while NMDA added alone had no effect. Glutamate decreased KAT-II mRNA level, which was attenuated by MK-801. The results suggest that stimulation of KAT-II expression during hepatic encephalopathy may be associated with a partial inactivation of astrocytic NMDAr by ammonia.

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Acknowledgments

The study was supported by grants NN401557340 (JA) and NN401130839 (JA) from the National Science Centre of the Republic of Poland.

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Correspondence to Marta Obara-Michlewska.

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Obara-Michlewska, M., Tuszyńska, P. & Albrecht, J. Ammonia upregulates kynurenine aminotransferase II mRNA expression in rat brain: a role for astrocytic NMDA receptors?. Metab Brain Dis 28, 161–165 (2013). https://doi.org/10.1007/s11011-012-9353-3

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  • DOI: https://doi.org/10.1007/s11011-012-9353-3

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