| First Author | Fan LM | Year | 2019 |
| Journal | J Clin Invest | Volume | 129 |
| Issue | 8 | Pages | 3374-3386 |
| PubMed ID | 31329158 | Mgi Jnum | J:282258 |
| Mgi Id | MGI:6369904 | Doi | 10.1172/JCI125173 |
| Citation | Fan LM, et al. (2019) Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature. J Clin Invest 129(8):3374-3386 |
| abstractText | 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 gammaH2AX; 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. |
