Nerve injury converts Schwann cells in a long-term repair-like state in human neuroma tissue.

Autor: Deininger S; Peripheral Nerve Surgery Unit, Department of Neurosurgery, Ulm University, District Hospital, 89312 Günzburg, Germany., Schumacher J; Institute of Neurobiochemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany., Blechschmidt A; Institute of Neurobiochemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany., Song J; Institute of Neurobiochemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany., Klugmann C; Institute of Neurobiochemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany., Antoniadis G; Peripheral Nerve Surgery Unit, Department of Neurosurgery, Ulm University, District Hospital, 89312 Günzburg, Germany., Pedro M; Peripheral Nerve Surgery Unit, Department of Neurosurgery, Ulm University, District Hospital, 89312 Günzburg, Germany., Knöll B; Institute of Neurobiochemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: bernd.knoell@uni-ulm.de., Meyer Zu Reckendorf S; Institute of Neurobiochemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: sofia.meyer-zu-reckendorf@uni-ulm.de.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Dec; Vol. 382, pp. 114981. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1016/j.expneurol.2024.114981
Abstrakt: Peripheral nerve injury (PNI) induces neuroma formation at the severed nerve stump resulting in impaired nerve regeneration and functional recovery in patients. So far, molecular mechanisms and cell types present in the neuroma impeding on regeneration have only sparsely been analyzed. Herein we compare resected human neuroma tissue with intact donor nerves from the same patient. Neuroma from several post-injury timepoints (1-13 months) were included, thereby allowing for temporal correlation with molecular and cellular processes. We observed reduced axonal area and percentage of myelin producing Schwann cells (SCs) compared to intact nerves. However, total SOX10 positive SC numbers were comparable. Notably, markers for SCs in a repair mode including c-JUN, the low-affinity neurotrophin receptor (NTR) p75, SHH (sonic hedgehog) and SC proliferation (phospho-histone H3) were upregulated in neuroma, suggesting presence of SCs in repair status. In agreement, in neuroma, pro-regenerative markers such as phosphorylated i.e. activated CREB (pCREB), ATF3, GAP43 and SCG10 were upregulated. In addition, neuroma tissue was infiltrated by several types of macrophages. Finally, when taken in culture, neuroma SCs were indistinguishable from controls SCs with regard to proliferation and morphology. However, cultured neuroma SCs retained a different molecular signature from control SCs including increased inflammation and reduced gene expression for differentiation markers such as myelin genes. In summary, human neuroma tissue consists of SCs with a repair status and is infiltrated strongly by several types of macrophages.
Competing Interests: Declaration of competing interest Declarations of interest: none.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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