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- W2897028869 abstract "As the population ages, dementia and aging-related diseases are becoming increasingly prevalent. Mounting evidence suggests that there are factors present in young blood that can counteract the effects of brain aging. Similarly, we have identified factors in aged blood whose increase with aging is associated with negative effects on cognition. Among these factors is eotaxin, a chemokine known to induce cognitive deficits in young wild-type mice and is implicated in aging-associated diseases such as Alzheimer's disease and Parkinson's disease. To test whether targeting the primary eotaxin receptor, CCR3, could prevent eotaxin-induced cognitive deficits, we treated young C57Bl/6 mice with recombinant eotaxin and co-administered a small molecule targeting the CCR3 receptor, twice a day for 18 days. In a second experiment, 23-month-old aged C57Bl/6 mice were treated with the CCR3 antagonist for 3 weeks to assess effects on aging-induced cognitive dysfunction driven in part by endogenous increases in eotaxin. We also treated young C57Bl/6 mice with LPS to induce brain inflammation, treated with the CCR3 antagonist, and assessed markers of peripheral and brain inflammation. CCR3 antagonist treatment significantly improved performance on the Y maze and Barnes maze tests for cognition in eotaxin-treated young mice. CCR3 antagonist treatment was also effective in reversing age-associated cognitive decline in aged mice with similar improvements in performance in the Y maze and Barnes maze tests. In addition, we found that the locomotor dysfunction observed in aged mice was improved with CCR3 antagonist treatment. We then investigated effects on neuroinflammation, and found that treatment with the CCR3 antagonist prevented the LPS-induced increase in microglial activation in the brain. These results implicate the potential therapeutic utility of CCR3 antagonism for improving neuroinflammation and cognition in aging-associated neurodegenerative diseases such as Alzheimer's disease." @default.
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- W2897028869 date "2018-07-01" @default.
- W2897028869 modified "2023-10-16" @default.
- W2897028869 title "P3‐043: TARGETING THE EOTAXIN/CCR3 PATHWAY IN AGING‐ASSOCIATED COGNITIVE DECLINE" @default.
- W2897028869 doi "https://doi.org/10.1016/j.jalz.2018.06.1398" @default.
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