title: Recovery of axonal myelination sheath and axonal caliber in the mouse corpus callosum following damage induced by N,N-diethyldithiocarbamate.
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.
authors: Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Avda/Diagonal 645, Barcelona, Spain.
authors: Juana
authors: J
authors: Utrera
authors: Rafael
authors: R
authors: Romero
authors: Ester
authors: E
authors: Verdaguer
authors: Fèlix
authors: F
authors: Junyent
authors: Carme
authors: C
authors: Auladell
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003337:Corpus Callosum / Q000187:drug effects* / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure*; D004050:Ditiocarb / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats
chemical_list: D000276:Adjuvants, Immunologic; D004050:Ditiocarb