Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL-10−/− Mice. Issue 9 (29th April 2022)

• Record Type: Journal Article
• Authors: Saleh, Nazaneen; Cosarderelioglu, Caglar; Vajapey, Ramya; Walston, Jeremy; Abadir, Peter M
• Editors: Anderson, Rozalyn M
• Is Part Of: Journals of gerontology. Volume 77:Issue 9(2022)
• Page Start: 1784
• Page End: 1788
• Publication Date: 2022-04-29
• Subjects: Angiotensin system -- Brain -- Inflammation -- Losartan -- Tau; Geriatrics -- Periodicals; Gerontology -- Periodicals; 618.97
• DOI: 10.1093/gerona/glac101
• Languages: English
• ISSNs: 1079-5006

Abstract

Abstract: Chronic inflammation, oxidative stress, and dysregulation of the renin–angiotensin system are closely linked, and their crosstalk commonly contributes to age-related physical and cognitive decline. The primary dementia-protective benefits of Angiotensin II type 1 receptor (AT1 R) blockers are believed to arise from systemic effects on blood pressure. However, there is an independently regulated brain-specific renin–angiotensin system. Here, we examined the impact of 4 weeks of oral Losartan treatment on the brains of aged (100 weeks old) IL-10 −/− mice, an animal model of chronic inflammation and frailty. Our data show that aged IL-10 −/− mice have higher AT1 R and Nitrotyrosine (oxidative stress marker) levels in their frontal cortex tissue but not in cerebellar or hippocampal tissue compared to age- and sex-matched wild type mice. Losartan treatment for 4 weeks is associated with lower AT1 R protein level, Nitrotyrosine, and Tau protein in the frontal cortex of aged IL-10 −/− mice. Our results highlight the impact of Losartan, an AT1 R blocker commonly prescribed for treating high blood pressure, on the brain-specific angiotensin system and AT1 R-linked downstream effects such as brain oxidative stress damage and Tau burden in a frailty mouse model.