title: Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits and motor impairment.
abstract: Dementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well-established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been increasingly suggested as therapeutic strategy against neurodegeneration, particularly in AD, there is controversial evidence about whether loss of Tau progressively impacts on motor function arguing about damage of CNS motor components. Using a variety of motor-related tests, we herein provide evidence of an age-dependent motor impairment in Tau-/- animals that is accompanied by ultrastructural and functional impairments of the efferent fibers that convey motor-related information. Specifically, we show that the sciatic nerve of old (17-22-months) Tau-/- mice displays increased degenerating myelinated fibers and diminished conduction properties, as compared to age-matched wild-type (Tau+/+) littermates and younger (4-6 months) Tau-/- and Tau+/+ mice. In addition, the sciatic nerves of Tau-/- mice exhibit a progressive hypomyelination (assessed by g-ratio) specifically affecting large-diameter, motor-related axons in old animals. These findings suggest that loss of Tau protein may progressively impact on peripheral motor system.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lopes
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: André
authors.initials: A
authors.lastname: Lopes
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Vítor
authors.initials: V
authors.lastname: Pinto
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Guimarães
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Vanessa Morais
authors.initials: VM
authors.lastname: Sardinha
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Duarte-Silva
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Pinheiro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Pizarro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: João Filipe
authors.initials: JF
authors.lastname: Oliveira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Leite-Almeida
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sotiropoulos
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009431:Neural Conduction / Q000502:physiology; D012584:Sciatic Nerve / Q000378:metabolism / Q000503:physiopathology*; D016875:tau Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D016875:tau Proteins
keywords: Tau; knockout; motor deficits; myelination; nerve conduction; peripheral nerve