Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature

Fan, Lampson M., Geng, Li, Cahill-Smith, Sarah, Liu, Fangfei, Douglas, Gillian, Mckenzie, Chris-Anne, Smith, Colin, Brooks, Gavin, Channon, Keith M. and Li, Jian-Mei (2019) Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature. Journal of Clinical Investigation, 129 (8). pp. 3374-3386. ISSN 0021-9738

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Abstract

Oxidative stress plays an important role in aging-related neurodegeneration. This study used littermates of WT and Nox2-knockout (Nox2KO) mice plus endothelial cell-specific human Nox2 overexpression-transgenic (HuNox2Tg) mice to investigate Nox2-derived ROS in brain aging. Compared with young WT mice (3-4 months), aging WT mice (20-22 months) had obvious metabolic disorders and loss of locomotor activity. Aging WT brains had high levels of angiotensin II (Ang II) and ROS production; activation of ERK1/2, p53, and γH2AX; and losses of capillaries and neurons. However, these abnormalities were markedly reduced in aging Nox2KO brains. HuNox2Tg brains at middle age (11-12 months) already had high levels of ROS production and activation of stress signaling pathways similar to those found in aging WT brains. The mechanism of Ang II-induced endothelial Nox2 activation in capillary damage was examined using primary brain microvascular endothelial cells. The clinical significance of Nox2-derived ROS in aging-related loss of cerebral capillaries and neurons was investigated using postmortem midbrain tissues of young (25-38 years) and elderly (61-85 years) adults. In conclusion, Nox2 activation is an important mechanism in aging-related cerebral capillary rarefaction and reduced brain function, with the possibility of a key role for endothelial cells.

Item Type: Article
Keywords: Aging, Apoptosis, Neurodegeneration, Neuroscience, endothelial cells
Depositing User: RED Unit Admin
Date Deposited: 21 Jan 2020 11:25
Last Modified: 21 Jan 2020 11:25
URI: http://bucks.repository.guildhe.ac.uk/id/eprint/17968

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