Mouse Bone Marrow-derived Microglia-like Cells Secrete Transforming Growth Factor-β1 and Promote Microglial Aβ Phagocytosis and Reduction of Brain Aβ

Neuroscience
Eriko KurodaKazuyuki Takata

Abstract

Accumulation of amyloid-β (Aβ) 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 Aβ phagocytosis. High levels of transforming growth factor-β1 (TGF-β1) were present in the conditioned medium, and BMDML cells and microglia expressed Tgf-β1 mRNA and TGF-β receptor type 1 (TGF-βR1) protein, respectively. BMDML conditioned medium also induced microglial Smad2/3 phosphorylation. A TGF-βR1 inhibitor suppressed Smad2/3 phosphorylation and promotion of microglial Aβ phagocytosis induced by conditioned medium. Recombinant mouse TGF-β1 similarly increased microglial Aβ phagocytosis and induced Smad2/3 phosphorylation, which were suppressed by the TGF-βR1 inhibitor. Brain TGF-β1 levels and resident microglial TGF-β1R expression were increased by intrahippocamp...Continue Reading

Citations

Jan 8, 2021·Frontiers in Aging Neuroscience·Zhengran YuXuenong Zou

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