1. Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature
- Author
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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
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Brain -- Comparative analysis ,Genetic engineering -- Comparative analysis ,Neurophysiology -- Comparative analysis ,Tumor proteins -- Comparative analysis ,Angiotensin II -- Comparative analysis ,Endothelium -- Comparative analysis ,Brain damage -- Comparative analysis ,Neurons -- Comparative analysis ,Oxidative stress ,Angiotensins ,Health care industry - 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 [gamma]H2AX; 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., Introduction The brain is a highly metabolic organ requiring a consistent supply of oxygen and nutrients for normal function. Ensuring a sufficient oxygen and nutrition supply to the brain is [...]
- Published
- 2019
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