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

Fan, L. M., Geng, L., Cahill-Smith, S., Liu, F., Douglas, G., Mckenzie, C.-A., Smith, C., Brooks, G., Channon, K. M. and Li, J.-m. ORCID: https://orcid.org/0000-0002-3294-3818 (2019) Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature. The Journal of Clinical Investigation, 129 (8). pp. 3374-3386. ISSN 1558-8238 doi: 10.1172/JCI125173

Abstract/Summary

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
URI	https://reading-clone.eprints-hosting.org/id/eprint/85419
Identification Number/DOI	10.1172/JCI125173
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Uncontrolled Keywords	Aging, Apoptosis, Neurodegeneration, Neuroscience, endothelial cells
Publisher	American Society for Clinical Investigation
Download/View statistics	View download statistics for this item