title: Axonal retraction and regeneration induced by N,N-diethyldithiocarbamate (DEDTC) in the central nervous system.
abstract: Dithiocarbamates (DTCs), such as disulfiram, have been used in aversion therapy for alcoholism even though an inherent toxicity is induced, which is related mainly to peripheral neuropathy and is associated with behavioural and neurological complications. At anatomical and histopathological levels, DTCs affect structural elements in nervous tissue, such as axonal degeneration and alterations in the cytoskeletal proteins of astrocytes. Therefore, given the axonal effects of DTCs and to gain further insight into axonal growth and axonal pathfinding in the central nervous system (CNS), here we established an in vivo experimental model of mouse development. Daily intraperitoneal injections of N,N-diethyldithiocarbamate (DEDTC), the first metabolite of disulfiram, were given from postnatal day 2 (P2) until P15. From P16 until P30, animals were not treated. Treatment induced considerable physiological alterations, such as growth delay, throughout postnatal development. Moreover, by immunohistochemistry techniques, we observed important alterations in the cytoskeletal glial protein at early stages of postnatal development. At later stages (P15), the immunoreactivity pattern detected by an antibody against axonal neurofilaments (anti-NF-H) showed alteration in the axonal distribution pattern followed by drastic axonal loss at P22, data that were corroborated using an anti-MBP (myelin basic protein) antibody. Using an antibody against the beta amyloid precursor protein (APP), we detected axonal injury. Furthermore, given that we observed axonal re-growth in adulthood in the in vivo model presented, we propose that this model would be a good system in which to identify new strategies for inducing regenerative growth in neural diseases in which axonal regeneration is blocked.
authors.affiliation: Departament de Biologia Cellular, Universitat de Barcelona, Diagonal 645, E-08028 Barcelona, Spain.
authors.forename: Fèlix
authors.initials: F
authors.lastname: Junyent
authors.forename: Juana
authors.initials: J
authors.lastname: Utrera
authors.forename: Carme
authors.initials: C
authors.lastname: Auladell
mesh_terms: D000375:Aging / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000931:Antidotes / Q000633:toxicity; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000031:analogs & derivatives* / Q000633:toxicity; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D004676:Myelin Basic Protein / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D000931:Antidotes; D003598:Cytoskeletal Proteins; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D009498:Neurotoxins; C051774:neurofilament protein H; D004050:Ditiocarb; C039353:dihydroxyethyldithiocarbamate