Subchronic N-acetylcysteine Treatment Decreases Brain Kynurenic Acid Levels and Improves Cognitive Performance in Mice
| Autor: | Paulina Ovalle Ovalle Rodríguez, Robert Schwarcz, Tonali Blanco Ayala, Gonzalo Pérez de la Cruz, Anabel Jiménez Anguiano, Daniela Ramírez Ortega, Dinora González González Esquivel, Korrapati V. Sathyasaikumar, Benjamín Pineda, Verónica Pérez de la Cruz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Physiology medicine.drug_class Metabolite Clinical Biochemistry Pharmacology Biochemistry Article Acetylcysteine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Kynurenic acid kynurenic acid Medicine Molecular Biology biology business.industry lcsh:RM1-950 Kynurenine aminotransferase II Cell Biology Receptor antagonist N-acetylcysteine kynurenine 030104 developmental biology lcsh:Therapeutics. Pharmacology chemistry Systemic administration biology.gene learning and memory business 030217 neurology & neurosurgery Kynurenine Ex vivo medicine.drug |
| Zdroj: | Antioxidants, Vol 10, Iss 147, p 147 (2021) Antioxidants Volume 10 Issue 2 |
| ISSN: | 2076-3921 |
| Popis: | The tryptophan (Trp) metabolite kynurenic acid (KYNA) is an &alpha 7-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&rsquo s key biosynthetic enzyme, and reduces KYNA neosynthesis in rats in vivo. In this study, we examined if repeated systemic administration of NAC influences brain KYNA and cognitive performance in mice. Animals received NAC (100 mg/kg, i.p.) daily for 7 days. Redox markers, KYNA levels, and KAT II activity were determined in the brain. We also assessed the effect of repeated NAC treatment on Trp catabolism using brain tissue slices ex vivo. Finally, learning and memory was evaluated with and without an acute challenge with KYNA&rsquo s bioprecursor L-kynurenine (Kyn 100 mg/kg). Subchronic NAC administration protected against an acute pro-oxidant challenge, decreased KYNA levels, and lowered KAT II activity and improved memory both under basal conditions and after acute Kyn treatment. In tissue slices from these mice, KYNA neosynthesis from Trp or Kyn was reduced. Together, our data indicate that prolonged treatment with NAC may enhance memory at least in part by reducing brain KYNA levels. |
| Databáze: | OpenAIRE |
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