Abstract
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.
Highlights
Aging and reduced exposure to environmental microbes can both potentiate neuroinflammatory responses
We examine whether M. vaccae immunization ameliorated features indicative of microglia priming/activation, including Iba[1] immunoreactivity and microglia density, in the aged rat brain
We investigated whether subcutaneous M. vaccae immunization mitigated age-associated changes in microglia morphology and gene expression markers
Summary
Aging and reduced exposure to environmental microbes can both potentiate neuroinflammatory responses. 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. The aging process is characterized by a progressive shift from a homeostatic balance of inflammatory markers towards a “primed” or sensitized state[2] This increased neuroinflammatory priming makes the aged brain further susceptible to the disruptive effects of intrinsic and extrinsic factors like disease, infection, and stress[3,4,5,6], thereby elevating the risk of affective disorders, cognitive impairments, and neurodegenerative diseases in the aged population[7, 8]. This morphology is associated with chemotaxis, secretion of pro-inflammatory cytokines such as IL-1β and tumor necrosis factor α, and phagocytosis
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