A prebiotic diet modulates microglia response and motor deficits in α-synuclein overexpressing mice

Output Details

Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.

Identifier (DOI)
10.5281/zenodo.6377704
Tags
  • Mouse
  • Postmortem

Meet the Authors

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    Joseph Boktor, BSc

    Key Personnel: Team Sulzer

    California Institute of Technology

  • John Bostick, PhD

    Key Personnel: Team Gradinaru Team Sulzer

    California Institute of Technology

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    Livia Hecke Morais, PhD

    Key Personnel: Team Sulzer Team Gradinaru

    California Institute of Technology

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    Gregory Humphrey

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    Ali Keshavarzian

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    Johnathan Katz

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    Matt Thomson

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    Rob Knight

  • Viviana Gradinaru, PhD

    Lead PI (Core Leadership): Team Gradinaru

    California Institute of Technology

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    Bruce Hamaker

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    Christopher Glass

  • Sarkis Mazmanian

    Co-PI (Core Leadership): Team Sulzer Team Gradinaru

    California Institute of Technology

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    Reem Abdel-Haq

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    Johannes Schlachetzki

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    Thaisa Cantu-Jungles

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    Taren Thron

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    Mengying Zhang

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    Tahmineh Khazaei

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    Sujatha Chilakala