Institute of Biology, Otto-von-Guericke University, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany.
Institute of Inflammation and Neurodegeneration, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany.
Brain Behav Immun. 2022 Jan;99:203-217. doi: 10.1016/j.bbi.2021.10.007. Epub 2021 Oct 18.
Antibiotics are widely applied for the treatment of bacterial infections, but their long-term use may lead to gut flora dysbiosis and detrimental effects on brain physiology, behavior as well as cognitive performance. Still, a striking lack of knowledge exists concerning electrophysiological correlates of antibiotic-induced changes in gut microbiota and behavior. Here, we investigated changes in the synaptic transmission and plasticity together with behaviorally-relevant network activities from the hippocampus of antibiotic-treated mice. Prolonged antibiotic treatment led to a reduction of myeloid cell pools in bone marrow, circulation and those surveilling the brain. Circulating Ly6C inflammatory monocytes adopted a proinflammatory phenotype with increased expression of CD40 and MHC II. In the central nervous system, microglia displayed a subtle activated phenotype with elevated CD40 and MHC II expression, increased IL-6 and TNF production as well as with an increased number of Iba1 + cells in the hippocampal CA3 and CA1 subregions. Concomitantly, we detected a substantial reduction in the synaptic transmission in the hippocampal CA1 after antibiotic treatment. In line, carbachol-induced cholinergic gamma oscillation were reduced upon antibiotic treatment while the incidence of hippocampal sharp waves was elevated. These alterations were associated with the global changes in the expression of neurotrophin nerve growth factor and inducible nitric oxide synthase, both of which have been shown to influence cholinergic system in the hippocampus. Overall, our study demonstrates that antibiotic-induced dysbiosis of the gut microbiome and subsequent alteration of the immune cell function are associated with reduced synaptic transmission and gamma oscillations in the hippocampus, a brain region that is critically involved in mediation of innate and cognitive behavior.
抗生素被广泛用于治疗细菌感染，但长期使用可能会导致肠道菌群失调，并对大脑生理、行为和认知表现产生不利影响。然而，人们对于抗生素引起的肠道菌群和行为变化的电生理相关性知之甚少。在这里，我们研究了抗生素处理小鼠的海马突触传递和可塑性的变化以及与行为相关的网络活动。长期抗生素治疗导致骨髓、循环和监测大脑的髓系细胞池减少。循环 Ly6C 炎性单核细胞表现出促炎表型，CD40 和 MHC II 的表达增加。在中枢神经系统中，小胶质细胞表现出轻微的激活表型，CD40 和 MHC II 的表达增加，IL-6 和 TNF 的产生增加，海马 CA3 和 CA1 区的 Iba1+细胞数量增加。同时，我们检测到抗生素处理后海马 CA1 区的突触传递明显减少。与此一致的是，抗生素处理后，乙酰胆碱诱导的胆碱能γ振荡减少，而海马尖波的发生率增加。这些改变与神经生长因子和诱导型一氧化氮合酶的表达的整体变化有关，这两者都被证明会影响海马中的胆碱能系统。总的来说，我们的研究表明，抗生素引起的肠道微生物失调和随后的免疫细胞功能改变与海马中的突触传递和γ振荡减少有关，海马是参与先天和认知行为调节的关键脑区。
