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Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling

Author

Listed:
  • Benjamin C. Creekmore

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Kathryn Kixmoeller

    (University of Pennsylvania
    University of Pennsylvania)

  • Ben E. Black

    (University of Pennsylvania
    University of Pennsylvania)

  • Edward B. Lee

    (University of Pennsylvania)

  • Yi-Wei Chang

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Ultrastructure of human brain tissue has traditionally been examined using electron microscopy (EM) following fixation, staining, and sectioning, which limit resolution and introduce artifacts. Alternatively, cryo-electron tomography (cryo-ET) allows higher resolution imaging of unfixed cellular samples while preserving architecture, but it requires samples to be vitreous and thin enough for transmission EM. Due to these requirements, cryo-ET has yet to be employed to investigate unfixed, never previously frozen human brain tissue. Here we present a method for generating lamellae in human brain tissue obtained at time of autopsy that can be imaged via cryo-ET. We vitrify the tissue via plunge-freezing and use xenon plasma focused ion beam (FIB) milling to generate lamellae directly on-grid at variable depth inside the tissue. Lamellae generated in Alzheimer’s disease brain tissue reveal intact subcellular structures including components of autophagy and potential pathologic tau fibrils. Furthermore, we reveal intact compact myelin and functional cytoplasmic expansions. These images indicate that plasma FIB milling with cryo-ET may be used to elucidate nanoscale structures within the human brain.

Suggested Citation

  • Benjamin C. Creekmore & Kathryn Kixmoeller & Ben E. Black & Edward B. Lee & Yi-Wei Chang, 2024. "Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47066-1
    DOI: 10.1038/s41467-024-47066-1
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    1. Zvonimir Vrselja & Stefano G. Daniele & John Silbereis & Francesca Talpo & Yury M. Morozov & André M. M. Sousa & Brian S. Tanaka & Mario Skarica & Mihovil Pletikos & Navjot Kaur & Zhen W. Zhuang & Zha, 2019. "Restoration of brain circulation and cellular functions hours post-mortem," Nature, Nature, vol. 568(7752), pages 336-343, April.
    2. Martin Meschkat & Anna M. Steyer & Marie-Theres Weil & Kathrin Kusch & Olaf Jahn & Lars Piepkorn & Paola Agüi-Gonzalez & Nhu Thi Ngoc Phan & Torben Ruhwedel & Boguslawa Sadowski & Silvio O. Rizzoli & , 2022. "White matter integrity in mice requires continuous myelin synthesis at the inner tongue," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Tristan Bepler & Kotaro Kelley & Alex J. Noble & Bonnie Berger, 2020. "Topaz-Denoise: general deep denoising models for cryoEM and cryoET," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    4. Casper Berger & Maud Dumoux & Thomas Glen & Neville B.-y. Yee & John M. Mitchels & Zuzana Patáková & Michele C. Darrow & James H. Naismith & Michael Grange, 2023. "Plasma FIB milling for the determination of structures in situ," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Yang Shi & Wenjuan Zhang & Yang Yang & Alexey G. Murzin & Benjamin Falcon & Abhay Kotecha & Mike Beers & Airi Tarutani & Fuyuki Kametani & Holly J. Garringer & Ruben Vidal & Grace I. Hallinan & Tammar, 2021. "Structure-based classification of tauopathies," Nature, Nature, vol. 598(7880), pages 359-363, October.
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