イベント/終了

【開催案内】KGRI Lecture Series: Regulation of a Aβ Amyloidosis and Neuroinflammation by the Gut Microbiome(2022.11.25開催)

2022.10.26

慶應義塾大学グローバルリサーチインスティテュート(KGRI)では、国際的な研究・教育交流を図ることを目的として、最先端の研究・教育に携わる方を国内外よりお招きして講演会を開催しています。

今回は、シカゴ大学よりSangram S. Sisodia先生をお招きして、「Regulation of a Aβ Amyloidosis and Neuroinflammation by the Gut Microbiome」と題して講演いただきます。

主 催:グローバルリサーチインスティテュート(KGRI)
日 時:2022年11月25日(金) 9:00-10:00
会 場:信濃町キャンパス総合医科学研究棟1階ラウンジ
開催⽅法︓対面
参加申込︓こちらよりお申し込みください
言 語:英語(同時通訳なし)

講演者:Professor Sangram S. Sisodia, Professor of Neurobiology, University of Chicago

講演概要:
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.

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