2021
DOI: 10.3390/antiox10020147
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Subchronic N-acetylcysteine Treatment Decreases Brain Kynurenic Acid Levels and Improves Cognitive Performance in Mice

Abstract: The tryptophan (Trp) metabolite kynurenic acid (KYNA) is an α7-nicotinic and N-methyl-d-aspartate receptor antagonist. Elevated brain KYNA levels are commonly seen in psychiatric disorders and neurodegenerative diseases and may be related to cognitive impairments. Recently, we showed that N-acetylcysteine (NAC) inhibits kynurenine aminotransferase II (KAT II), KYNA’s key biosynthetic enzyme, and reduces KYNA neosynthesis in rats in vivo. In this study, we examined if repeated systemic administration of NAC inf… Show more

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Cited by 20 publications
(21 citation statements)
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“…N -acetylcysteine (NAC) can inhibit the formation of kynurenic acid through inhibition of KAT-2 [ 117 ]. Although this can improve cognitive function [ 118 ], low placental KAT-2 expression deems it unlikely for NAC to have placental effects. Furthermore, NAC also has broad anti-oxidant effects, making it difficult to establish whether potential effects of NAC are mediated through inhibition of KAT-2.…”
Section: Pharmacological Interventionsmentioning
confidence: 99%
“…N -acetylcysteine (NAC) can inhibit the formation of kynurenic acid through inhibition of KAT-2 [ 117 ]. Although this can improve cognitive function [ 118 ], low placental KAT-2 expression deems it unlikely for NAC to have placental effects. Furthermore, NAC also has broad anti-oxidant effects, making it difficult to establish whether potential effects of NAC are mediated through inhibition of KAT-2.…”
Section: Pharmacological Interventionsmentioning
confidence: 99%
“…Ultimately, the deficits in glutamatergic and GABAergic neuromodulation in relation to KYNA elevation in EKyn young adult offspring bridge our understanding between KYNA and neuromodulatory deficits which may contribute to the observed impairments in cognition, sleep, and arousal (21,26,27). In conclusion, sex-specific neurochemical changes observed in this study highlight the importance of evaluating sex as a biological variable when considering therapeutics strategies, including inhibition of KAT II to inhibit KYNA synthesis (48,67,68), and improve behavioral dysfunction and clinical outcomes for individuals suffering from psychiatric disorders.…”
Section: Discussionmentioning
confidence: 55%
“…ROS were evaluated through DCF-DA oxidation [ 35 ]. Briefly, 125 µL of forebrain homogenates previously incubated with FeSO 4 and kynurenines were mixed with DCF-DA solution (final concentration: 75 µM), then incubated under dark conditions at 37 °C for 30 min.…”
Section: Methodsmentioning
confidence: 99%
“…According to a previous report, LP was assessed in forebrain homogenates by the determination of TBA-reactive substances (TBA-RS) [ 35 ]. After incubation with FeSO 4 and kynurenines, 125 µL of the brain homogenate were mixed with 250 μL of the TBA reagent (containing 0.375 g of TBA + 15 g of trichloroacetic acid + 2.54 mL of HCl) and incubated in a boiling water bath (94 °C) for 20 min.…”
Section: Methodsmentioning
confidence: 99%
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