Balog Emma, Jenei Gyula, Berkó Anikó Magyariné, Lőrinczi Bálint, Szatmári István, Vécsei László, Toldi József, Kis Zsolt
Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Neurosci Lett. 2025 Apr 1;854:138220. doi: 10.1016/j.neulet.2025.138220. Epub 2025 Mar 26.
Kynurenic acid (KYNA) is one of the main neuroprotective substances of the kynurenine pathway. KYNA plays an important role in various neurodegenerative and psychiatric diseases. Although KYNA has been shown to have neuroprotective effects, it cannot be used as a peripherally administered drug due to its poor ability to cross the blood-brain barrier. To address this limitation, chemically modified KYNA analogues are being developed: SZR72 is one such analogue and has been shown to be protective in various animal models. Glutamate-induced excitotoxicity is a key factor in many neurodegenerative diseases. Therefore, we used the N-methyl-D-aspartate (NMDA)-induced excitotoxicity model to investigate the neuromodulatory agents. Using acute hippocampal slices from mouse brains, we investigated the potential neuroprotective effect of KYNA and its analogue, SZR72 on NMDA-induced excitotoxicity across different age groups of mice. The degree of tissue damage was assessed using biochemical and histological methods. In young animals (1- and 4-week-old), NMDA treatment caused no significant changes, and the cells were found to be resistant. However, in older animals (8-week-old and 1-year-old), NMDA caused significant damage in cells and tissue structure, which was reduced by KYNA and SZR72 treatment. To our knowledge, this is the first study to compare the neuroprotective effects of KYNA and SZR72 in animals of different ages using an in vitro NMDA excitotoxicity model.
犬尿喹啉酸（KYNA）是犬尿氨酸途径的主要神经保护物质之一。KYNA在各种神经退行性疾病和精神疾病中发挥着重要作用。尽管已证明KYNA具有神经保护作用，但由于其穿越血脑屏障的能力较差，不能用作外周给药药物。为了解决这一局限性，正在开发化学修饰的KYNA类似物：SZR72就是这样一种类似物，并且已证明在各种动物模型中具有保护作用。谷氨酸诱导的兴奋性毒性是许多神经退行性疾病的关键因素。因此，我们使用N-甲基-D-天冬氨酸（NMDA）诱导的兴奋性毒性模型来研究神经调节药物。利用小鼠脑的急性海马切片，我们研究了KYNA及其类似物SZR72对不同年龄组小鼠NMDA诱导的兴奋性毒性的潜在神经保护作用。使用生化和组织学方法评估组织损伤程度。在幼龄动物（1周龄和4周龄）中，NMDA处理未引起显著变化，并且发现细胞具有抗性。然而，在老龄动物（8周龄和1岁）中，NMDA对细胞和组织结构造成了显著损伤，而KYNA和SZR72处理可减轻这种损伤。据我们所知，这是第一项使用体外NMDA兴奋性毒性模型比较KYNA和SZR72在不同年龄动物中的神经保护作用的研究。
