Losartan Mitigates Oxidative Stress in the Brains of Aged IL10-/- Mice. (17th December 2021)

• Record Type: Journal Article
• Authors: Saleh, Nazaneen; Cosarderelioglu, Caglar; Abadir, Peter M; Vajapey, Ramya; Walston, Jeremy D
• Is Part Of: Innovation in aging. Volume 5(2021)Supplement 1
• Page Start: 684
• Page End: 684
• Publication Date: 2021-12-17
• Subjects: Aging -- Periodicals; Gerontology -- Periodicals; 612.67
• DOI: 10.1093/geroni/igab046.2553
• Languages: English
• ISSNs: 2399-5300

Abstract

Abstract: Chronic inflammation has been linked to frailty and declined cognition in older adults. Activation of the renin-angiotensin system (RAS) through the angiotensin Type1 receptor (AT1R) has been suggested as a contributory factor that links both inflammation and aging. Here we examined the impact of 4 weeks of oral Losartan treatment on IL10-/- mice brains, a mouse model of chronic inflammation and frailty. Frontal cortex, cerebellar, and hippocampal tissue of aged (100 weeks old) male IL10-/- mice were studied. Western blot techniques were employed to quantify changes in brain AT1R, nitrotyrosine (NT) as an oxidative stress marker, and Tau proteins. Our data show that aged IL-10 mice have significantly higher levels of AT1R in the cortex tissue but not in cerebellar or hippocampal tissue compared to age and sex-matched WT mice (0.63 + 0.35 vs 1.5 + 0.54, WT vs IL10, respectively, P<0.004). When treated with LOS, brain cortical tissue of IL10 -/- mice showed significant decreases in levels of AT1R (1.5 + 0.54 vs 0.98 + 0.50, IL10 vs LOS treated IL10, respectively, P<0.04), NT (0.72 + 0.12 vs 0.42 + 0.10, IL10 vs LOS treated IL10, respectively, P<0.009), and Tau protein (1.3 + 0.31 vs 0.15 + 0.08, IL10 vs LOS treated IL10, respectively, P<0.004) as compared to control IL10-/- mice. Losartan treatment had no significant effect on hippocampal AT1R or NT levels. Our results highlight the impact of Losartan, a drug commonly prescribed for the treatment of high blood pressure, on the brain-specific angiotensin system and its downstream effects on brain oxidative stress and Tau pathology.