Department of Pharmacology and Toxicology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, Poland.
Int J Mol Sci. 2023 Apr 1;24(7):6617. doi: 10.3390/ijms24076617.
Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively. A 10-min incubation of astrocytes with 1-5 mM butyrate increased the ATP gliotransmitter release by 78% (95%CI: 45-119%), < 0.001. The effect was found to be mediated by the cytosolic Ca mobilization. Both 10-min and 24-h treatments with indole-3-propionic acid produced no significant effects on the release of gliotransmitters. The results for glutamate release were inconclusive due to a specific glutamate release pattern discovered in the tested model. This preliminary report of butyrate-induced ATP gliotransmitter release appears to provide a novel mechanistic explanation for the beneficial effect of this gut microbiota metabolite on brain function; however, the results require further evaluation in more composed models.
丁酸和吲哚-3-丙酸是中枢神经系统可利用的肠道微生物群代谢物，它们对人类大脑功能具有潜在的有益影响，目前正在作为抗抑郁药进行测试。星形胶质细胞是肠道代谢物的潜在作用靶点之一；然而，丁酸和吲哚-3-丙酸的作用机制尚未完全阐明。为了验证这一机制，我们用化合物或不用化合物处理人星形胶质细胞系培养物，并使用发光和荧光方法分别收集上清液，以分析 ATP 和谷氨酸神经递质的释放。用 1-5 mM 的丁酸处理星形胶质细胞 10 分钟，可使 ATP 神经递质释放增加 78%（95%CI：45-119%），<0.001。该效应是通过细胞质 Ca2+动员介导的。用吲哚-3-丙酸处理 10 分钟和 24 小时对神经递质的释放均无显著影响。由于在测试模型中发现了特定的谷氨酸释放模式，因此谷氨酸释放的结果尚无定论。本研究初步报告了丁酸诱导的 ATP 神经递质释放，似乎为这种肠道微生物群代谢物对大脑功能的有益影响提供了新的机制解释；然而，这些结果需要在更复杂的模型中进一步评估。
