| First Author | Geng L | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 1582 |
| PubMed ID | 32005915 | Mgi Jnum | J:355590 |
| Mgi Id | MGI:7750986 | Doi | 10.1038/s41598-020-58422-8 |
| Citation | Geng L, et al. (2020) Nox2 dependent redox-regulation of microglial response to amyloid-beta stimulation and microgliosis in aging. Sci Rep 10(1):1582 |
| abstractText | Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid beta (Abeta) plays a crucial role in Alzheimer's disease. However, the mechanism of Abeta-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 Abeta peptide 1-42 (Abeta(42)) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Abeta(42) markedly induced BV2 cell ROS production, Nox2 expression, p47(phox) and ERK1/2 phosphorylation, cell proliferation and IL-1beta 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, Abeta deposition, microgliosis and IL-1beta 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-1beta 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 Abeta(42) stimulation and in aging-associated microgliosis and brain inflammation. |
