Study helps better understand the development of adolescent brain
The next experiment was aimed at evaluating the lifespan of the activated ILC2s in young and old mouse brains. They found that while both had the same proliferative capacity, the latter are more long-lived. They also seem to return to their quiescent state after the period of proliferation, when the stressor (IL-33) is withdrawn. This may account for their greater persistence following exposure to this cytokine, since quiescent cells suffer less DNA damage and other types of cell injury. Responsive to secondary stimulation
However, the fact that their burst of proliferative activity died down after the stimulus was stopped did not affect their ability to be re-stimulated, as proved by a third experiment in which the aged mice were again treated with IL-33 for 2 days. This led to vigorous proliferation again. The scientists concluded that ILC2s in older mouse brains can switch between a state of dormancy and proliferation which allows them to live longer, which in turn is responsible for their gradual build-up with time. Longer proliferation
Not only so, this self-renewing capability is greater in ILC2s from older mice, as they continued to multiply vigorously for 4 weeks without showing any features of exhaustion, in contrast to the two-week proliferation period of ILC2s from younger mice. They produce large amounts of functional proteins characteristic of these cells as well as of self-renewing stem cells.
Eventually, however, these cells begin to show signs of aging, but lymphocyte exhaustion marker proteins are reduced and remain low over time in these cells from aged mice. Improved cognitive performance
Cognitive ability also improved in these treated mice, as well as in older mice treated with already activated ILC2s transferred into the cerebral ventricles, compared to ILC2s from younger mice. Researcher Kristen L. Zuloaga says, “This suggested that activated ILC2 can improve the cognitive function of aged mice.”
An interesting finding was that ILC2s from the choroid plexus in aged mice were more vigorous in their proliferative and functional renewal characteristics than those from the meninges, though both were at higher levels than those in younger mice. Effects mediated by IL-5
When the researchers looked at the proteins secreted by activated ILC2s, they found that one of them was the cytokine IL-5. When old mice were treated with this chemical separately, their brains showed new nerve cells forming in the hippocampus, and a lower level of inflammation in the brain. This included a higher production of anti-inflammatory chemicals, a lower expression of pro-inflammatory cytokines, and a lower number of CD8 T cells that promote inflammation. The pro-inflammatory cytokine TNFα was also reduced, and its downstream signaling molecules. The number of and level of activation of the brain immune cells called microglia was also reduced. This probably leads a lower potential for damage. The scientists comment, “Together, IL-5 may directly act on aging-associated pro-inflammatory T cells to restrain neuroinflammation, which may lead to enhanced neurogenesis and improved cognitive function.”
Cognitive ability was found to be higher in this experimental group as well over a broad range of tests. “Together,” say the researchers, “our results highlight a novel role for IL-5 in alleviating aging-associated cognitive decline.” Implications
In summary, the study concludes, “Our work has thus revealed the accumulation of tissue-resident ILC2 cells in the choroid plexus of aged brains and demonstrated that their activation may revitalize the aged brain and alleviate aging-associated cognitive decline.” The researchers think their work may lay the foundation for a new approach to preventing age-related damage to the brain that is responsible for several cognitive and degenerative disorders linked to neurologic injury. Journal reference:
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