[Information] KGRI Lecture Series: Regulation of a Aβ Amyloidosis and Neuroinflammation by the Gut Microbiome (November 25, 2022)
2022.10.26Keio University Global Research Institute (KGRI) aims to promote international research and educational exchange and invites those working in the forefront of research and education in Japan and overseas to give lectures.
This time, Professor Sangram S. Sisodia, Professor of Neurobiology at the University of Chicago, will give a lecture titled " Regulation of a Aβ Amyloidosis and Neuroinflammation by the Gut Microbiome "
Host: Keio University Global Research Institute (KGRI)
Date & Time: Friday, November 25, 2022 9:00-10:00
Venue: 1F Lounge, Center for Integrated Medical Research, Shinanomachi Campus, Keio University
Format: In-person
Registration: Click here to register
Language: English
Speaker: Professor Sangram S. Sisodia (Professor of Neurobiology, University of Chicago)
Abstract:
Background: We have explored the role of the gut microbiome on Aβ deposition and microglial transcriptomes in transgenic mouse models of Aβ amyloidosis using antibiotic (ABX)-mediated perturbations of the gut microbiota. In parallel, we have established germ-free transgenic mice that are devoid of microbiota
Methods: We orally administered an antibiotic cocktail either postnatally or throughout life to induce sustained alterations in gut microbial populations in two mouse models of Abeta amyloidosis. Using well-established IHC, biochemical and transcriptional readouts, we have evaluated amyloid deposition and neuroinflammation in these paradigms.
Result: We demonstrate that ABX-mediated alterations in the microbiome parallel changes in plasma cytokines and chemokines, reductions in amyloid deposition and modulation of morphological and transcriptional landscapes of microglia that is selective for male animals. Importantly, reintroduction of fecal matter (FMT) into ABX-treated male mice restores amyloid pathology, neurodegenerative phenotypes and transcriptional changes to levels that observed in vehicle-treated mice. Using a CSF1 receptor antagonist, we now establish that microglia play a critical role in modulation of these phenotypes. The presentation will include studies of female mice subject to ovariectomy and ABX treatment to assess the role of ovarian hormones in mediating the documented sex-specific effects of gut microbiome perturbations on Aβ deposition and microglial phenotypes.
Conclusion: Our studies reveal sex-specific alterations in amyloid deposition and microglial phenotypes in transgenic mice upon treatment with orally administered ABX.
Acknowledgments: This work was supported by Cure Alzheimer's Fund (CAF), Open Philanthropy Fund, Alzheimer's Association and Good Ventures Foundation. SSS is a paid Consultant of AZTherapies Inc. and Green Valley Therapeutics, Inc.
For inquiries about this event:
School of Medicine, Department of Physiology (ext. 62613)
