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Recovery of axonal myelination sheath and axonal caliber in the mouse corpus callosum following damage induced by N,N-diethyldithiocarbamate

Authors

  • Juana Utrera,

    1. Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Avda/Diagonal 645, Barcelona, Spain
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  • Rafael Romero,

    1. Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
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  • Ester Verdaguer,

    1. Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Avda/Diagonal 645, Barcelona, Spain
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  • Fèlix Junyent,

    1. Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, Spain
    2. Unitat de Bioquímica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain
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    • F.J. and C.A. contributed equally to this work.

  • Carme Auladell

    1. Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Avda/Diagonal 645, Barcelona, Spain
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    • F.J. and C.A. contributed equally to this work.


Carme Auladell, as above.
E-mail: cauladell@ub.edu

Abstract

Disulfiram is an aldehyde dehydrogenase inhibitor used for the treatment of alcohol dependence and of cocaine addiction. It has been demonstrated that subchronic administration of disulfiram or N,N-diethyldithiocarbamate (DEDTC), the main derivative of disulfiram, to rats can produce central–peripheral distal axonopathy. However, few data regarding the axonal effects of these compounds in the central nervous system exist. Our previous studies have revealed DEDTC-induced axonal damage in the mouse brain during the course of postnatal development, together with alterations in axonal pathfinding and in the myelination process, with partial recovery during the post-treatment period. In order to gather new data about how this axonal damage and recovery occurs in the central nervous system, we performed an ultrastructural analysis of the axons located in the corpus callosum from mice treated with DEDTC during postnatal development. The axonal caliber throughout the axonal area, the maximum axonal diameter, the maximum fiber diameter, and the axonal circularity, at different postnatal stages [from postnatal day (P)9 to P30], were analyzed. In addition, parameters related to the myelinization process (number of myelinated axons, sheath thickness, and the ratio of myelinated axons to total axons) were evaluated. A reduction in the average value of axonal caliber during treatment and a delay in the axonal myelination process were detected. Whereas early recovery of individual axons occurred after treatment (P22), complete recovery of myelinated axons occurred at late postnatal stages (P42). Therefore, chronic treatment with dithiocarbamates requires periods of rest to encourage the recovery of myelinated axons.

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