
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.22.609215
preprint
1
Article
Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy
Shiers Stephanie http://orcid.org/0000-0002-9646-1850

Mazhar Khadijah
Wangzhou Andy
Haberberger Rainer V
Lesnak Joseph B
Sankaranarayanan Ishwarya
Tavares-Ferreira Diana http://orcid.org/0000-0003-0986-3630

Cervantes Anna
Funk Geoffrey
Horton Peter
Vines Erin
Dussor Gregory
Price Theodore J http://orcid.org/0000-0002-6971-6221

23 8 2024
2024.08.22.609215https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.22.609215
nihpp-2024.08.22.609215.pdf
Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invaded Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings solve a 100-year mystery of the nature of Nageotte nodules linking these pathological structures to pain and sensory loss in DPN.
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pmc
