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Ground state depletion microscopy as a tool for studying microglia-synapse interactions.

Patrick Jarmo Paasila1, Sandra Y Y Fok2, Neftali Flores-Rodriguez3

  • 1Faculty of Medicine and Health, Charles Perkins Centre and School of Medical Sciences, The University of Sydney, Camperdown, NSW, Australia.

Journal of Neuroscience Research
|March 8, 2021
PubMed
Summary

Ground state depletion followed by individual molecule return microscopy (GSDIM) now visualizes nanoscale protein distribution in archival human brain tissue. This super-resolution technique offers cost-effective insights into cell interactions, particularly in dementia research.

Keywords:
Alzheimer diseaseRRID:AB_141874RRID:AB_2199013RRID:AB_2286948RRID:AB_2534072RRID:AB_2534076RRID:AB_2535731RRID:AB_2536183RRID:AB_2633277RRID:AB_324660RRID:AB_839504RRID:SCR_001622RRID:SCR_002285RRID:SCR_002798RRID:SCR_013673RRID:SCR_013726ground state depletion followed by individual molecule return microscopymicrogliapost-mortem archival human brain tissuesuper-resolution microscopysynapseszebrafish

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Microscopy

Background:

  • Ground state depletion followed by individual molecule return microscopy (GSDIM) is a super-resolution technique.
  • Previous applications focused on living cells to study nanoscale protein co-localization.
  • Archival human brain tissue analysis using GSDIM was previously limited.

Purpose of the Study:

  • To demonstrate the successful application of GSDIM to archival human brain tissue sections.
  • To visualize nanoscale interactions between cellular components in situ.
  • To establish GSDIM as a viable, cost-effective alternative to electron microscopy for archival tissue analysis.

Main Methods:

  • Application of GSDIM to archival human brain tissue sections, including Alzheimer's disease cases.
  • Analysis of experimental tissue samples from mouse and zebrafish larvae.
  • Utilizing antibodies for molecular imaging with super-resolution microscopy.

Main Results:

  • Successful visualization of presynaptic terminals and microglia at nanoscale resolution.
  • Clearer insights into in situ interactions between microglia and presynaptic terminals.
  • Demonstration of GSDIM's applicability to routine formalin-fixed paraffin-embedded human brain sections.

Conclusions:

  • GSDIM can be effectively applied to archival human brain tissue, including disease cases.
  • This method provides high-resolution insights into cellular interactions beyond diffraction limits.
  • GSDIM offers a time- and cost-efficient alternative to electron microscopy for archival tissue research, particularly for studying microglia-synapse interactions in dementia.