Super-resolution imaging pinpoints the periodic ultrastructure at the human node of Ranvier and its disruption in patients with polyneuropathy
Appeltshauser, Luise ; Linke, Janis ; Heil, Hannah S LU
; Karus, Christine
; Schenk, Joachim
; Hemmen, Katherina
; Sommer, Claudia
; Doppler, Kathrin
and Heinze, Katrin G
(2023)
In Neurobiology of Disease
182.
- Abstract
The node of Ranvier is the key element in saltatory conduction along myelinated axons, but its specific protein organization remains elusive in the human species. To shed light on nanoscale anatomy of the human node of Ranvier in health and disease, we assessed human nerve biopsies of patients with polyneuropathy by super-resolution fluorescence microscopy. We applied direct stochastic optical reconstruction microscopy (dSTORM) and supported our data by high-content confocal imaging combined with deep learning-based analysis. As a result, we revealed a ∼ 190 nm periodic protein arrangement of cytoskeletal proteins and axoglial cell adhesion molecules in human peripheral nerves. In patients with polyneuropathy, periodic distances... (More)
The node of Ranvier is the key element in saltatory conduction along myelinated axons, but its specific protein organization remains elusive in the human species. To shed light on nanoscale anatomy of the human node of Ranvier in health and disease, we assessed human nerve biopsies of patients with polyneuropathy by super-resolution fluorescence microscopy. We applied direct stochastic optical reconstruction microscopy (dSTORM) and supported our data by high-content confocal imaging combined with deep learning-based analysis. As a result, we revealed a ∼ 190 nm periodic protein arrangement of cytoskeletal proteins and axoglial cell adhesion molecules in human peripheral nerves. In patients with polyneuropathy, periodic distances increased at the paranodal region of the node of Ranvier, both at the axonal cytoskeleton and at the axoglial junction. In-depth image analysis revealed a partial loss of proteins of the axoglial complex (Caspr-1, neurofascin-155) in combination with detachment from the cytoskeletal anchor protein ß2-spectrin. High content analysis showed that such paranodal disorganization occurred especially in acute and severe axonal neuropathy with ongoing Wallerian degeneration and related cytoskeletal damage. We provide nanoscale and protein-specific evidence for the prominent, but vulnerable role of the node of Ranvier for axonal integrity. Furthermore, we show that super-resolution imaging can identify, quantify and map elongated periodic protein distances and protein interaction in histopathological tissue samples. We thus introduce a promising tool for further translational applications of super resolution microscopy.
(Less)
- author
- Appeltshauser, Luise
; Linke, Janis
; Heil, Hannah S
LU
; Karus, Christine
; Schenk, Joachim
; Hemmen, Katherina
; Sommer, Claudia
; Doppler, Kathrin
and Heinze, Katrin G
- publishing date
- 2023-06-15
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, Ranvier's Nodes/metabolism, Axons/metabolism, Cytoskeletal Proteins/metabolism, Peripheral Nerves/metabolism, Polyneuropathies
- in
- Neurobiology of Disease
- volume
- 182
- article number
- 106139
- publisher
- Academic Press
- external identifiers
-
- pmid:37146836
- scopus:85159342046
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2023.106139
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
- id
- 490cf252-ffba-4237-8c0a-bbceec8af322
- date added to LUP
- 2025-04-07 16:07:59
- date last changed
- 2025-07-15 11:40:03
@article{490cf252-ffba-4237-8c0a-bbceec8af322,
abstract = {{<p>The node of Ranvier is the key element in saltatory conduction along myelinated axons, but its specific protein organization remains elusive in the human species. To shed light on nanoscale anatomy of the human node of Ranvier in health and disease, we assessed human nerve biopsies of patients with polyneuropathy by super-resolution fluorescence microscopy. We applied direct stochastic optical reconstruction microscopy (dSTORM) and supported our data by high-content confocal imaging combined with deep learning-based analysis. As a result, we revealed a ∼ 190 nm periodic protein arrangement of cytoskeletal proteins and axoglial cell adhesion molecules in human peripheral nerves. In patients with polyneuropathy, periodic distances increased at the paranodal region of the node of Ranvier, both at the axonal cytoskeleton and at the axoglial junction. In-depth image analysis revealed a partial loss of proteins of the axoglial complex (Caspr-1, neurofascin-155) in combination with detachment from the cytoskeletal anchor protein ß2-spectrin. High content analysis showed that such paranodal disorganization occurred especially in acute and severe axonal neuropathy with ongoing Wallerian degeneration and related cytoskeletal damage. We provide nanoscale and protein-specific evidence for the prominent, but vulnerable role of the node of Ranvier for axonal integrity. Furthermore, we show that super-resolution imaging can identify, quantify and map elongated periodic protein distances and protein interaction in histopathological tissue samples. We thus introduce a promising tool for further translational applications of super resolution microscopy.</p>}},
author = {{Appeltshauser, Luise and Linke, Janis and Heil, Hannah S and Karus, Christine and Schenk, Joachim and Hemmen, Katherina and Sommer, Claudia and Doppler, Kathrin and Heinze, Katrin G}},
issn = {{0969-9961}},
keywords = {{Humans; Ranvier's Nodes/metabolism; Axons/metabolism; Cytoskeletal Proteins/metabolism; Peripheral Nerves/metabolism; Polyneuropathies}},
language = {{eng}},
month = {{06}},
publisher = {{Academic Press}},
series = {{Neurobiology of Disease}},
title = {{Super-resolution imaging pinpoints the periodic ultrastructure at the human node of Ranvier and its disruption in patients with polyneuropathy}},
url = {{http://dx.doi.org/10.1016/j.nbd.2023.106139}},
doi = {{10.1016/j.nbd.2023.106139}},
volume = {{182}},
year = {{2023}},
}