As people age past 50, their brains begin to decrease in mass. But even as neurons shrink, other brain cells appear to become more active. Microglia — the small immune cells that sense injury and the presence of pathogens in the nervous system — have shown increased activity, producing higher amounts of signaling molecules called cytokines and leading researchers to suggest that these cells may become dysfunctional as our brains get older. Because higher levels of cytokines have been associated with neurodegenerative diseases, scientists are paying close attention to the role of microglia in these disorders.
Now, research by Rockefeller University scientists shows that microglia in the brains of older mice are just as functional as those of younger animals, possibly even more so. Their research, published in the journal Glia by postdoctoral fellow Amanda Sierra, graduate fellow Andrés Gottfried, research associate professor Karen Bulloch, and Alfred E. Mirsky Professor Bruce McEwen concludes that although the aging microglia had elevated levels of cytokines, they reacted to an immune-system challenge with proportionally the same response as those in younger brains.
“The microglia of the old mice seem to be more active — as indicated by the higher levels of cytokines they produce when they’re in the resting state — versus those in young animals,” says Gottfried, a student in McEwen’s lab who graduated in June. But when they presented the cells with an immune challenge, a molecule called LPS that’s known to trigger an immune-system reaction, the older microglia increased their activity by the same proportion as the younger ones. The functioning and responsiveness of the cells themselves appeared to be intact in the aging brain.
Because older microglia started out at a higher rate of activity, however, their overall cytokine levels were higher. “Which means that the impact of having an infection may be greater on the older animal or older person,” says McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology. In turn, that could mean that the same dose of certain anti-inflammatory drugs given to older patients might have a different result than it would in someone younger.
The scientists also found no discernable difference in cytokine production between genders, something that surprised them since the incidence and progression of neurodegenerative diseases tend to be much greater in women, especially after menopause. One suggested cause for this is low levels of circulating estrogen, but Bulloch and her colleagues also compared microglial activity in mice that had no ovaries, and therefore lacked estrogen, with normal mice. Again, they found no significant difference.
“This is in agreement with our previous findings,” Gottfried says, “which showed that estrogen doesn’t influence the microglia response, although it probably makes a difference in other cell types in the brain.” Other hormones do affect microglial cells, McEwen says, but it’s unclear how the cells’ reactions to those hormones change with age.
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