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Lack of galectin-3 speeds Wallerian degeneration by altering TLR and pro-inflammatory cytokine expressions in injured sciatic nerve

Authors

  • Bruno Siqueira Mietto,

    1. Laboratório de Neurodegeneração e Reparo, Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Sofia Jurgensen,

    1. Laboratório de Neurodegeneração e Reparo, Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Lucinéia Alves,

    1. Laboratório de Neurodegeneração e Reparo, Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Cyntia Pecli,

    1. Laboratório de Imunofarmacologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Marcelo Sampaio Narciso,

    1. Laboratório de Neurodegeneração e Reparo, Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Iranaia Assunção-Miranda,

    1. Laboratório de Resposta Celular á Infecções Virais, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Dea Maria Serra Villa-Verde,

    1. Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil
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  • Flávia Regina de Souza Lima,

    1. Laboratório de Morfogênese Celular, Programa de Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • João Ricardo Lacerda de Menezes,

    1. Laboratório de Neuroanatomia Celular, Programa de Anatomia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Cláudia Farias Benjamim,

    1. Laboratório de Imunofarmacologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Marcelo Torres Bozza,

    1. Laboratório de Inflamação e Imunidade, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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  • Ana Maria Blanco Martinez

    Corresponding author
    • Laboratório de Neurodegeneração e Reparo, Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Correspondence: Ana Maria Blanco Martinez, as above.

E-mail: martinez@histo.ufrj.br

Abstract

Wallerian degeneration (WD) comprises a series of events that includes activation of non-neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin-3 (Gal-3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following sciatic nerve crush in Gal-3−/− mice. Using an in vivo model of nerve degeneration, we observed that removal of myelin debris is more efficient in Gal-3−/− than in wild-type (WT) mice; we next used an in vitro phagocytosis assay to document that the phagocytic potential of macrophages and Schwann cells was enhanced in the Gal-3−/− mice. Moreover, both RNA and protein levels for the pro-inflammatory cytokines IL-1β and TNF-α, as well as for Toll-like receptor (TLR)-2 and -4, show robust increases in injured nerves from Gal-3−/−mice compared to those from WT mice. Collectively, these data indicate that the lack of Gal-3 results in an augmented inflammatory profile that involves the TLR–cytokine pathway, and increases the phagocytic capacity of Schwann cells and macrophages, which ultimately contributes to speeding the course of WD.

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