• Neuroscience · Jul 2020

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

    • Eriko Kuroda, Kaneyasu Nishimura, Shohei Kawanishi, Mari Sueyoshi, Fumitaka Ueno, Yumiko Toji, Naoko Abo, Toko Konishi, Koki Harada, Shiho Satake, Chiaki Shima, Yuki Toda, Yoshihisa Kitamura, Shun Shimohama, Eishi Ashihara, and Kazuyuki Takata.
    • Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
    • Neuroscience. 2020 Jul 1; 438: 217-228.

    AbstractAccumulation 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 intrahippocampal injection of BMDML cells in a mouse model of AD. Cotreatment with the TGF-βR1 inhibitor suppressed the ability of transplanted BMDML cells to increase microglial TGF-β1R expression and decrease hippocampal Aβ levels. Taken together, these findings suggested that transplanted BMDML cells secreted TGF-β1 to stimulate Aβ phagocytosis by resident microglia and decrease brain Aβ pathology.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

Want more great medical articles?

Keep up to date with a free trial of metajournal, personalized for your practice.
1,624,503 articles already indexed!

We guarantee your privacy. Your email address will not be shared.