Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature
Lampson M. Fan, … , Keith M. Channon, Jian-Mei Li
Lampson M. Fan, … , Keith M. Channon, Jian-Mei Li
Published July 22, 2019
Citation Information: J Clin Invest. 2019;129(8):3374-3386. https://doi.org/10.1172/JCI125173.
View: Text | PDF
Research Article Aging Neuroscience Article has an altmetric score of 4

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

  • Text
  • PDF
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.

Authors

Lampson M. Fan, Li Geng, Sarah Cahill-Smith, Fangfei Liu, Gillian Douglas, Chris-Anne Mckenzie, Colin Smith, Gavin Brooks, Keith M. Channon, Jian-Mei Li

×

Figure 2

Aging-related changes in WT and Nox2KO mouse midbrains.

Options: View larger image (or click on image) Download as PowerPoint
Aging-related changes in WT and Nox2KO mouse midbrains.
(A) ROS producti...
(A) ROS production by mouse midbrain sections detected by DHE fluorescence. Tiron was used to confirm the detection of O2•–. *P < 0.05 for indicated values versus young DHE values; †P < 0.05 for indicated values versus DHE values in the same age group. Fluo-intensity, fluorescence intensity. (B) Cerebral microvascular density. Capillaries were labeled with LE-lectin (FITC, green) and quantified. (C) Neuronal density. Neurons were labeled with NeuN (Cy3, red) and quantified. Nuclei were labeled with DAPI (blue in B and C). n = 6 mice/per group. Scale bars: 100 μm. (D) Dopaminergic neuron firing frequency. Left panels: Representative recording traces of aging brains. Right panels: Statistical analysis. n = 14 cells from 6 mice. *P < 0.05 for indicated values versus young values in the same genetic group; †P < 0.05 for indicated values versus aging WT values. Statistical analysis was performed using 1-way ANOVA followed by Bonferroni’s post hoc tests.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 7 X users
57 readers on Mendeley
See more details