| First Author | McKee CA | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 1796 |
| PubMed ID | 35110643 | Mgi Jnum | J:324404 |
| Mgi Id | MGI:6865108 | Doi | 10.1038/s41598-022-05862-z |
| Citation | McKee CA, et al. (2022) Astrocytes deficient in circadian clock gene Bmal1 show enhanced activation responses to amyloid-beta pathology without changing plaque burden. Sci Rep 12(1):1796 |
| abstractText | An emerging link between circadian clock function and neurodegeneration has indicated a critical role for the molecular clock in brain health. We previously reported that deletion of the core circadian clock gene Bmal1 abrogates clock function and induces cell-autonomous astrocyte activation. Regulation of astrocyte activation has important implications for protein aggregation, inflammation, and neuronal survival in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we investigated how astrocyte activation induced by Bmal1 deletion regulates astrocyte gene expression, amyloid-beta (Abeta) plaque-associated activation, and plaque deposition. To address these questions, we crossed astrocyte-specific Bmal1 knockout mice (Aldh1l1-Cre(ERT2);Bmal1(fl/fl), termed BMAL1 aKO), to the APP/PS1-21 and the APP(NL-G-F) models of Abeta accumulation. Transcriptomic profiling showed that BMAL1 aKO induced a unique transcriptional profile affecting genes involved in both the generation and elimination of Abeta. BMAL1 aKO mice showed exacerbated astrocyte activation around Abeta plaques and altered gene expression. However, this astrogliosis did not affect plaque accumulation or neuronal dystrophy in either model. Our results demonstrate that the striking astrocyte activation induced by Bmal1 knockout does not influence Abeta deposition, which indicates that the effect of astrocyte activation on plaque pathology in general is highly dependent on the molecular mechanism of activation. |
