| First Author | Shippy DC | Year | 2022 |
| Journal | BMC Genomics | Volume | 23 |
| Issue | 1 | Pages | 183 |
| PubMed ID | 35247975 | Mgi Jnum | J:321884 |
| Mgi Id | MGI:7255066 | Doi | 10.1186/s12864-022-08417-8 |
| Citation | Shippy DC, et al. (2022) Transcriptional response of murine microglia in Alzheimer's disease and inflammation. BMC Genomics 23(1):183 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and is the most common cause of late-onset dementia. Microglia, the primary innate immune cells of the central nervous system (CNS), have a complex role in AD neuropathology. In the initial stages of AD, microglia play a role in limiting pathology by removing amyloid-beta (Abeta) by phagocytosis. In contrast, microglia also release pro-inflammatory cytokines and chemokines to promote neuroinflammation and exacerbate AD neuropathology. Therefore, investigating microglial gene networks could identify new targets for therapeutic strategies for AD. RESULTS: We identified 465 differentially expressed genes (DEG) in 5XFAD versus wild-type mice by microarray, 354 DEG in lipopolysaccharide (LPS)-stimulated N9 microglia versus unstimulated control cells using RNA-sequencing (RNA-seq), with 32 DEG common between both datasets. Analyses of the 32 common DEG uncovered numerous molecular functions and pathways involved in Abeta phagocytosis and neuroinflammation associated with AD. Furthermore, multiplex ELISA confirmed the induction of several cytokines and chemokines in LPS-stimulated microglia. CONCLUSIONS: In summary, AD triggered multiple signaling pathways that regulate numerous genes in microglia, contributing to Abeta phagocytosis and neuroinflammation. Overall, these data identified several regulatory factors and biomarkers in microglia that could be useful in further understanding AD neuropathology. |
