title: Tau hyperphosphorylation and axonal damage induced by N,N-diethyldithiocarbamate (DEDTC) treatment along late postnatal development is followed by a rescue during adulthood.
abstract: Axonal degeneration has been described as the pathological hallmark of peripheral neuropathies induced by DEDTC. In addition, axonal damage has also been observed in the brain of mice treated daily with DEDTC along postnatal development, though with this experimental model there was observed to be axonal recovery after treatment, during the adulthood. To focus on this axonal dynamic activity, damage-recovery, a key axonal protein, the microtubule associated protein tau, was analyzed in this DEDTC model. Tau is a phosphoprotein and its dynamic site-specific phosphorylation is essential for its proper function; in fact, high levels are correlated with cell dysfunction. Furthermore, the levels of tau phosphorylation are associated with dynamic microtubules during periods of high plasticity. Thus, phosphorylated tau at two sites of phosphorylation, Ser(199) and Ser(396), were evaluated during the second week of postnatal development and throughout adulthood. The results obtained by Western blot made it evident that the levels of p-tau Ser(199) and p-tau Ser(396) were higher in treated mice than in controls. Interestingly, by immunohistochemistry there was shown to be an increase in p-tau-immunolabeling in neuronal soma together with axonal tract alterations in treated animals with respect to controls, and the analyses of GSK3 beta and cdk5 revealed an increase in its activity in DEDTC-treated animals. Nevertheless, in the adult a general decline in p-tau was observed together with a rescue of axonal tract. All these data support the idea that the axonal damage induced by DEDTC treatment along postnatal development is followed by an axonal rescue during adulthood.
authors.affiliation: Departament de Biologia Cellular, Facultat Biologia, Universitat Barcelona, Barcelona, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Utrera
authors.forename: Felix
authors.initials: F
authors.lastname: Junyent
authors.forename: Luisa
authors.initials: L
authors.lastname: de Lemos
authors.forename: Merce
authors.initials: M
authors.lastname: Pallàs
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero
authors.forename: Carme
authors.initials: C
authors.lastname: Auladell
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D002614:Chelating Agents / Q000633:toxicity; D051360:Cyclin-Dependent Kinase 5 / Q000187:drug effects / Q000378:metabolism; D004050:Ditiocarb / Q000031:analogs & derivatives* / Q000633:toxicity; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D020127:Recovery of Function / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D014855:Wallerian Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D016875:tau Proteins / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D016875:tau Proteins; D012694:Serine; D004050:Ditiocarb; D051360:Cyclin-Dependent Kinase 5; D000071679:Glycogen Synthase Kinase 3 beta; C495906:Cdk5 protein, mouse; D038362:Glycogen Synthase Kinase 3; C039353:dihydroxyethyldithiocarbamate