Journal Article

FZJ-2023-04873

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis

Kohle, F. (Corresponding author) ; Ackfeld, R. ; Klein, I. ; Svačina, M. K. R. ; Schneider, C. ; van Beers, T. ; Grandoch, A. ; Fink, G. R.FZJ* ; Lehmann, H. C. ; Barham, M.

2023
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neulet.2023.137456  doi:10.34734/FZJ-2023-04873

Abstract: Objective: We evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy.Methods: Experimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control.Results: No enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor.Conclusion: Our findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis.Keywords: Autoimmune neuropathy; Brain-derived neurotrophic factor; Drug repurposing; Guillain-Barré syndrome; Mitochondrial uncoupler; Neuroregeneration.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)

Appears in the scientific report 2023

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Database coverage:
; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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