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Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging
- Source :
- Scientific Reports, Geng, L, Fan, L M, Liu, F, Smith, C & Li, J 2020, ' Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging ', Scientific Reports, vol. 10, no. 1 . https://doi.org/10.1038/s41598-020-58422-8, Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
- Publication Year :
- 2019
-
Abstract
- Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ42) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ42 markedly induced BV2 cell ROS production, Nox2 expression, p47phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ42 stimulation and in aging-associated microgliosis and brain inflammation.
- Subjects :
- Adult
Male
medicine.medical_specialty
Aging
lcsh:Medicine
Inflammation
Stimulation
Pathogenesis
Microgliosis
Biochemistry
Article
chemistry.chemical_compound
Mice
Internal medicine
medicine
Animals
Humans
lcsh:Science
Neuroinflammation
Aged
chemistry.chemical_classification
Aged, 80 and over
Mice, Knockout
Reactive oxygen species
Multidisciplinary
Amyloid beta-Peptides
Microglia
Cell growth
Superoxide
lcsh:R
Middle Aged
Peptide Fragments
Mice, Inbred C57BL
medicine.anatomical_structure
Endocrinology
chemistry
Microscopy, Fluorescence
NADPH Oxidase 2
lcsh:Q
Female
medicine.symptom
Reactive Oxygen Species
Oxidation-Reduction
Neuroscience
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....18c50715f7a08df42f5ea1465a2c5393