Rosell-Cardona Cristina, Collins Michael K, O'Riordan Kenneth J, Goodson Michael S, Kelley-Loughnane Nancy, Cryan John F, Clarke Gerard
APC Microbiome Ireland, University College Cork, Cork, Ireland.
APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Neuropharmacology. 2025 Aug 1;273:110434. doi: 10.1016/j.neuropharm.2025.110434. Epub 2025 Mar 26.
Acute stress can enhance or impair synaptic plasticity depending on the nature, duration, and type of stress exposure as well as the brain region examined. The absence of a gut microbiome can also alter hippocampal plasticity. However, the possible interplay between synaptic plasticity, acute stress, and the gut microbiota remains unknown. Here, we examine this interaction and determine whether the gut microbiota impacts stress-induced alterations in hippocampal plasticity. Further, we explored whether exposure to the microbial metabolite butyrate is sufficient to counteract stress-induced alterations in synaptic plasticity. We used electrophysiological and molecular experiments in adult male C57/BL6 antibiotic-treated and acutely stressed mice. In electrophysiological experiments we treated hippocampal slices with 3 μM sodium butyrate to explore the effect of this microbial metabolite. We found the presence of the microbiota essential for the enhancement of both short- and long-term potentiation induced by 15 min of acute restraint stress. Furthermore, butyrate exposure effectively restored the stress-induced enhancement of potentiation in slices from microbiome-depleted animals while also enhancing long-term potentiation independent of stress. In addition, alterations of hippocampal synaptic plasticity markers were noted. Our findings highlight a critical new temporal role for gut-derived metabolites in defining the impact of acute stress on synaptic plasticity.
急性应激可增强或损害突触可塑性，这取决于应激暴露的性质、持续时间和类型以及所检测的脑区。肠道微生物群的缺失也会改变海马体的可塑性。然而，突触可塑性、急性应激和肠道微生物群之间可能的相互作用仍不清楚。在这里，我们研究这种相互作用，并确定肠道微生物群是否会影响应激诱导的海马体可塑性变化。此外，我们还探讨了暴露于微生物代谢产物丁酸盐是否足以抵消应激诱导的突触可塑性变化。我们在成年雄性C57/BL6抗生素处理和急性应激的小鼠身上进行了电生理和分子实验。在电生理实验中，我们用3 μM丁酸钠处理海马切片，以探究这种微生物代谢产物的作用。我们发现微生物群的存在对于由15分钟急性束缚应激诱导的短期和长期增强都是必不可少的。此外，丁酸盐暴露有效地恢复了微生物群缺失动物切片中应激诱导的增强，同时也增强了与应激无关的长期增强。此外，还观察到海马突触可塑性标记物的变化。我们的研究结果突出了肠道衍生代谢产物在定义急性应激对突触可塑性影响方面的一个关键新的时间作用。
