The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 Str., 05-110 Jablonna, Poland.
Int J Mol Sci. 2024 Aug 30;25(17):9428. doi: 10.3390/ijms25179428.
Kynurenic acid (KYNA), a tryptophan metabolite, is believed to exert neuromodulatory and neuroprotective effects in the brain. This study aimed to examine KYNA's capacity to modify gene expression and the activity of cellular antioxidant enzymes in specific structures of the sheep brain. Anestrous sheep were infused intracerebroventricularly with two KYNA doses-lower (4 × 5 μg/60 μL/30 min, KYNA20) and higher (4 × 25 μg/60 μL/30 min, KYNA100)-at 30 min intervals. The abundance of superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPx1) mRNA, as well as enzyme activities, were determined in the medial-basal hypothalamus (MBH), the preoptic (POA) area of the hypothalamus, and in the hippocampal CA1 field. Both doses of KYNA caused a decrease ( < 0.01) in the expression of SOD2 and CAT mRNA in all structures examined compared to the control group (except for CAT in the POA at the KYNA100 dose). Furthermore, lower levels of SOD2 mRNA ( < 0.05) and CAT mRNA ( < 0.01) were found in the MBH and POA and in the POA and CA, respectively, in sheep administered with the KYNA20 dose. Different stimulatory effects on GPx1 mRNA expression were observed for both doses ( < 0.05- < 0.01). KYNA exerted stimulatory but dose-dependent effects on SOD2, CAT, and GPx1 activities ( < 0.05- < 0.001) in all brain tissues examined. The results indicate that KYNA may influence the level of oxidative stress in individual brain structures in sheep by modulating the expression of genes and the activity of at least SOD2, CAT, and GPx1. The present findings also expand the general knowledge about the potential neuroprotective properties of KYNA in the central nervous system.
犬尿酸（KYNA）是一种色氨酸代谢物，据信在大脑中具有神经调节和神经保护作用。本研究旨在检查 KYNA 改变绵羊特定脑结构中基因表达和细胞抗氧化酶活性的能力。在 30 分钟的间隔内，用 KYNA 两种剂量（低剂量：4×5μg/60μL/30min，KYNA20；高剂量：4×25μg/60μL/30min，KYNA100）经脑室灌注对乏情绵羊进行处理。测定了中-基底下丘脑（MBH）、下丘脑视前区（POA）和海马 CA1 区的超氧化物歧化酶 2（SOD2）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶 1（GPx1）mRNA 的丰度以及酶活性。与对照组相比（除了在高剂量的 KYNA 时 POA 中的 CAT），两种剂量的 KYNA 都导致所有检测结构中 SOD2 和 CAT mRNA 的表达降低（<0.01）。此外，与对照组相比，在接受 KYNA20 剂量的绵羊中，MBH 和 POA 以及 POA 和 CA 中 SOD2 mRNA 水平较低（<0.05）和 CAT mRNA 水平较低（<0.01）。两种剂量均观察到对 GPx1 mRNA 表达的不同刺激作用（<0.05-<0.01）。KYNA 对所有检测的脑组织中 SOD2、CAT 和 GPx1 活性（<0.05-<0.001）均表现出刺激作用，但呈剂量依赖性。研究结果表明，KYNA 通过调节基因表达和至少 SOD2、CAT 和 GPx1 的活性，可能影响绵羊各脑区的氧化应激水平。本研究结果还扩展了关于 KYNA 在中枢神经系统中潜在神经保护特性的一般认识。
