High-fat diet worsens the impact of aging on microglial function and morphology in a region-specific manner.

Hippocampal microglia are vulnerable to the effects of aging, displaying a primed phenotype and hyper-responsiveness to various stimuli. We have previously shown that short-term high-fat diet (HFD) significantly impairs hippocampal- and amygdala-based cognitive function in the aged without affecting it in the young. Here, we assessed if morphological and functional changes in microglia might be responsible for this. We analyzed hippocampus and amygdala from young and aging rats that had been given three days HFD, a treatment sufficient to cause both hippocampal- and amygdala-dependent cognitive and neuroinflammatory differences in the aged. Aging led to the expected priming of hippocampal microglia in that it increased microglial numbers and reduced branching in this region. Aging also increased microglial phagocytosis of microbeads in the hippocampus, but the only effect of HFD in this region was to increase the presence of enlarged synaptophysin boutons in the aged, indicative of neurodegeneration. In the amygdala, HFD exacerbated the effects of aging on microglial priming (morphology) and markedly suppressed phagocytosis without notably affecting synaptophysin. These data reveal that, like the hippocampus, the amygdala displays aging-related microglial priming. However, the microglia in this region are also uniquely vulnerable to the detrimental effects of short-term HFD in aging.