| First Author | Kuroda E | Year | 2020 |
| Journal | Neuroscience | Volume | 438 |
| Pages | 217-228 | PubMed ID | 32522344 |
| Mgi Jnum | J:293057 | Mgi Id | MGI:6445695 |
| Doi | 10.1016/j.neuroscience.2020.05.004 | Citation | Kuroda E, et al. (2020) Mouse Bone Marrow-derived Microglia-like Cells Secrete Transforming Growth Factor-beta1 and Promote Microglial Abeta Phagocytosis and Reduction of Brain Abeta. Neuroscience 438:217-228 |
| abstractText | Accumulation of amyloid-beta (Abeta) in brain tissue contributes to the pathophysiology of Alzheimer's disease (AD). We recently reported that intrahippocampal transplantation of mouse bone marrow-derived microglia-like (BMDML) cells suppresses brain amyloid pathology and cognitive impairment in a mouse model of AD. How these transplanted cells interact with resident microglia remains unknown. In the present study, we evaluated the effects of cytokines secreted from mouse BMDML cells on cultured mouse microglia. Conditioned medium from BMDML cells increased microglial Abeta phagocytosis. High levels of transforming growth factor-beta1 (TGF-beta1) were present in the conditioned medium, and BMDML cells and microglia expressed Tgf-beta1 mRNA and TGF-beta receptor type 1 (TGF-betaR1) protein, respectively. BMDML conditioned medium also induced microglial Smad2/3 phosphorylation. A TGF-betaR1 inhibitor suppressed Smad2/3 phosphorylation and promotion of microglial Abeta phagocytosis induced by conditioned medium. Recombinant mouse TGF-beta1 similarly increased microglial Abeta phagocytosis and induced Smad2/3 phosphorylation, which were suppressed by the TGF-betaR1 inhibitor. Brain TGF-beta1 levels and resident microglial TGF-beta1R expression were increased by intrahippocampal injection of BMDML cells in a mouse model of AD. Cotreatment with the TGF-betaR1 inhibitor suppressed the ability of transplanted BMDML cells to increase microglial TGF-beta1R expression and decrease hippocampal Abeta levels. Taken together, these findings suggested that transplanted BMDML cells secreted TGF-beta1 to stimulate Abeta phagocytosis by resident microglia and decrease brain Abeta pathology. |
