Translational Neurobiology and Disease Modelling Laboratory, Department of Life Sciences, School of Natural Sciences, Shiv Nadar Institution of Eminence, Greater Noida, 201314, India.
Int Immunopharmacol. 2024 Jun 30;135:112295. doi: 10.1016/j.intimp.2024.112295. Epub 2024 May 21.
Aspartame, an artificial sweetener, is consumed by millions of people globally. There are multiple reports of aspartame and its metabolites affecting cognitive functions in animal models and humans, which include learning problems, headaches, seizures, migraines, irritable moods, anxiety, depression, and insomnia. These cognitive deficits and associated symptoms are partly attributed to dysregulated excitatory and inhibitory neurotransmitter balance due to aspartate released from aspartame, resulting in an excitotoxic effect in neurons, leading to neuronal damage. However, microglia, a central immunocompetent cell type in brain tissue and a significant player in inflammation can contribute to the impact. Microglia rapidly respond to changes in CNS homeostasis. Aspartame consumption might affect the microglia phenotype directly via methanol-induced toxic effects and indirectly via aspartic acid-mediated excitotoxicity, exacerbating symptoms of cognitive decline. Long-term oral consumption of aspartame thus might change microglia's phenotype from ramified to activated, resulting in chronic or sustained activation, releasing excess pro-inflammatory molecules. This pro-inflammatory surge might lead to the degeneration of healthy neurons and other glial cells, impairing cognition. This review will deliberate on possible links and research gaps that need to be explored concerning aspartame consumption, ecotoxicity and microglia-mediated inflammatory cognitive impairment. The study covers a comprehensive analysis of the impact of aspartame consumption on cognitive function, considering both direct and indirect effects, including the involvement of microglia-mediated neuroinflammation. We also propose a novel intervention strategy involving tryptophan supplementation to mitigate cognitive decline symptoms in individuals with prolonged aspartame consumption, providing a potential solution to address the adverse effects of aspartame on cognitive function.
阿斯巴甜是一种人工甜味剂，全球有数以百万计的人在食用。有多项报告表明，阿斯巴甜及其代谢物会影响动物模型和人类的认知功能，包括学习问题、头痛、癫痫发作、偏头痛、烦躁不安、焦虑、抑郁和失眠。这些认知缺陷和相关症状部分归因于由于阿斯巴甜释放的天冬氨酸导致兴奋性和抑制性神经递质平衡失调，从而产生神经元的兴奋毒性作用，导致神经元损伤。然而，小胶质细胞是脑组织中一种重要的免疫活性细胞类型，也是炎症的重要参与者，它也可能对这种影响起到作用。小胶质细胞会迅速对中枢神经系统内环境的变化做出反应。阿斯巴甜的消耗可能会通过甲醇诱导的毒性作用直接影响小胶质细胞的表型，也可能通过天冬氨酸介导的兴奋毒性作用间接影响小胶质细胞的表型，从而加剧认知能力下降的症状。因此，长期口服阿斯巴甜可能会使小胶质细胞的表型从分枝状转变为激活状，导致慢性或持续激活，释放过多的促炎分子。这种促炎反应可能导致健康神经元和其他神经胶质细胞的退化，从而损害认知功能。本综述将详细讨论有关阿斯巴甜消耗、生态毒性和小胶质细胞介导的炎症性认知障碍之间可能存在的联系和需要探索的研究空白。该研究全面分析了阿斯巴甜消耗对认知功能的影响，包括直接和间接影响，以及小胶质细胞介导的神经炎症的参与。我们还提出了一种新的干预策略，即补充色氨酸，以减轻长期食用阿斯巴甜的个体的认知下降症状，为解决阿斯巴甜对认知功能的不良影响提供了一种潜在的解决方案。
