Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA.
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, 80309, USA.
Sci Rep. 2022 Feb 9;12(1):2165. doi: 10.1038/s41598-022-05275-y.
Aging and reduced exposure to environmental microbes can both potentiate neuroinflammatory responses. Prior studies indicate that immunization with the immunoregulatory and anti-inflammatory bacterium, Mycobacterium vaccae (M. vaccae), in aged rats limits neuroimmune activation and cognitive impairments. However, the mechanisms by which M. vaccae immunization ameliorates age-associated neuroinflammatory "priming" and whether microglia are a primary target remain unclear. Here, we investigated whether M. vaccae immunization protects against microglia morphological changes in response to aging. Adult (3 mos) and aged (24 mos) Fisher 344 × Brown Norway rats were immunized with either M. vaccae or vehicle once every week for 3 weeks. Aging led to elevated Iba1 immunoreactivity, microglial density, and deramification of microglia processes in the hippocampus and amygdala but not other brain regions. Additionally, aged rats exhibited larger microglial somas in the dorsal hippocampus, suggestive of a more activated phenotype. Notably, M. vaccae treatment ameliorated indicators of microglia activation in both the amygdala and hippocampus. While changes in morphology appeared to be region-specific, gene markers indicative of microglia activation were upregulated by age and lowered in response to M. vaccae in all brain regions evaluated. Taken together, these data suggest that peripheral immunization with M. vaccae quells markers of age-associated microglia activation.
衰老和减少接触环境微生物都可能增强神经炎症反应。先前的研究表明，给老年大鼠接种免疫调节和抗炎细菌结核分枝杆菌（M. vaccae）可以限制神经免疫激活和认知障碍。然而，M. vaccae 免疫接种改善与年龄相关的神经炎症“启动”的机制以及小胶质细胞是否是主要靶标尚不清楚。在这里，我们研究了 M. vaccae 免疫接种是否可以防止小胶质细胞形态变化对衰老的反应。成年（3 个月）和老年（24 个月）Fisher 344×Brown Norway 大鼠每周用 M. vaccae 或载体免疫一次，共 3 周。衰老导致海马体和杏仁核中 Iba1 免疫反应性、小胶质细胞密度和小胶质细胞突起的去分支增加，但其他脑区没有。此外，老年大鼠在背侧海马体中表现出更大的小胶质细胞体，表明其具有更活跃的表型。值得注意的是，M. vaccae 处理改善了杏仁核和海马体中小胶质细胞激活的指标。虽然形态变化似乎具有区域特异性，但在所有评估的脑区中，年龄会上调指示小胶质细胞激活的基因标志物，并对 M. vaccae 产生反应而下调。综上所述，这些数据表明，用 M. vaccae 进行外周免疫接种可以抑制与年龄相关的小胶质细胞激活的标志物。
