Dai Ruanxian, Duan Zhantao, Han Bin, Chen Guobing, Wang Fuping, Shi Zhuange, Zhou Xian, Song Haifei, Ma Li, Meng Qiang
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
Department of Emergency, The First People's Hospital of Yunnan Province, Kunming, China.
Front Neurosci. 2025 Jun 2;19:1561291. doi: 10.3389/fnins.2025.1561291. eCollection 2025.
Mushroom poisoning represents a significant food safety issue globally, particularly neurotoxic mushroom poisoning, which raises considerable concern due to its potential to induce central nervous system symptoms. Ibotenic acid is identified as the primary neurotoxin associated with this form of poisoning; however, the underlying mechanisms of its neurotoxicity remain poorly understood.
This study aims to systematically evaluate the effects of ibotenic acid exposure across three consecutive key time points, from intoxication to recovery, on neurotransmitters related to the GABA/Glutamic-Acid, dopaminergic, serotonergic, and cholinergic systems in five brain regions: the cerebral cortex, hippocampus, striatum, brain stem, and cerebellum.
Through behavioral tests, we assessed the effects of ibotenic acid exposure on voluntary activities and learning and memory functions in mice. Additionally, we analyzed the changes in neurotransmitter concentrations across different brain regions using targeted metabolomics.
Behavioral results indicated that the total movement distance and speed in the open field test were significantly reduced, while the resting time was prolonged in the ibotenic acid-exposed group ( < 0.0001). The results of targeted metabolomics demonstrated that, compared to the control group, levels of glutamic acid in the hippocampus and brain stem significantly decreased after 4 h of ibotenic acid exposure ( < 0.05, < 0.001). Additionally, epinephrine levels in the cerebral cortex decreased at 20 min ( < 0.05), while tyrosine levels in the brain stem and cerebellum decreased after 4 h ( < 0.05). In the brain stem region, the tryptophan levels in each exposure group decreased significantly compared with the 4-h exposure group ( < 0.01), and brain stem choline levels significantly decreased ( < 0.05). Conversely, homovanillic acid levels in the brain stem increased ( < 0.01).
Preliminary studies have demonstrated that acute exposure to ibotenic acid inhibits motor activity but does not significantly affect learning and memory in mice. Exposure to ibotenic acid induces alterations in GABA/Glutamic-Acid, dopaminergic, serotonergic, and neurotransmitters associated with the cholinergic system in the brains of mice, with the most pronounced changes occurring in the brain stem region, exhibiting time-dependent and region-specific effects. This study offers new insights into the neurotoxic mechanisms of ibotenic acid.
蘑菇中毒是全球一个重大的食品安全问题，尤其是神经毒性蘑菇中毒，因其有可能引发中枢神经系统症状而备受关注。鹅膏蕈氨酸被确定为与这种中毒形式相关的主要神经毒素；然而，其神经毒性的潜在机制仍知之甚少。
本研究旨在系统评估从中毒到恢复的三个连续关键时间点暴露于鹅膏蕈氨酸对五个脑区（大脑皮层、海马体、纹状体、脑干和小脑）中与γ-氨基丁酸/谷氨酸、多巴胺能、5-羟色胺能和胆碱能系统相关的神经递质的影响。
通过行为测试，我们评估了暴露于鹅膏蕈氨酸对小鼠自主活动以及学习和记忆功能的影响。此外，我们使用靶向代谢组学分析了不同脑区神经递质浓度的变化。
行为结果表明，在旷场试验中，暴露于鹅膏蕈氨酸的组的总移动距离和速度显著降低，而静止时间延长（<0.0001）。靶向代谢组学的结果表明，与对照组相比，暴露于鹅膏蕈氨酸4小时后，海马体和脑干中的谷氨酸水平显著降低（<0.05，<0.001）。此外，大脑皮层中的肾上腺素水平在20分钟时降低（<0.05），而脑干和小脑中的酪氨酸水平在4小时后降低（<0.05）。在脑干区域，与4小时暴露组相比，各暴露组中的色氨酸水平显著降低（<0.01），脑干胆碱水平显著降低（<0.05）。相反，脑干中的高香草酸水平升高（<0.01）。
初步研究表明，急性暴露于鹅膏蕈氨酸会抑制小鼠的运动活动，但对学习和记忆没有显著影响。暴露于鹅膏蕈氨酸会导致小鼠大脑中γ-氨基丁酸/谷氨酸、多巴胺能、5-羟色胺能以及与胆碱能系统相关的神经递质发生改变，其中脑干区域的变化最为明显，呈现出时间依赖性和区域特异性效应。本研究为鹅膏蕈氨酸的神经毒性机制提供了新的见解。
