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Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits and motor impairment

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Resumo: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 (4-6months) 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.
Autores principais:Lopes, Sofia Oliveira
Outros Autores:Lopes, André Teixeira; Pinto, Vítor Manuel Silva; Guimarães, Marco Rafael; Sardinha, Vanessa Alexandra Morais; Silva, Sara Duarte; Pinheiro, Sara Isabel Santos; Pizarro, João Pedro Rodrigues; Oliveira, João F.; Sousa, Nuno; Leite-Almeida, Hugo; Sotiropoulos, Ioannis
Assunto:Tau Motor deficits Peripheral nerve Myelination Nerve conduction Knockout.
Ano:2016
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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