Cargando…
Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice
BACKGROUND: Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer’s disease (A...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880070/ https://www.ncbi.nlm.nih.gov/pubmed/24344647 http://dx.doi.org/10.1186/2051-5960-1-82 |
_version_ | 1782298039460823040 |
---|---|
author | Hoffmann, Nadine A Dorostkar, Mario M Blumenstock, Sonja Goedert, Michel Herms, Jochen |
author_facet | Hoffmann, Nadine A Dorostkar, Mario M Blumenstock, Sonja Goedert, Michel Herms, Jochen |
author_sort | Hoffmann, Nadine A |
collection | PubMed |
description | BACKGROUND: Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer’s disease (AD), synaptic failure and cognitive decline correlate best with the grade of tau-pathology. To address synaptic alterations in tauopathies, we analyzed the effects of mutant tau expression on excitatory postsynapses in vivo. RESULTS: Here we followed the fate of single dendritic spines in the neocortex of a tauopathy mouse model, expressing human P301S mutated tau, for a period of two weeks. We observed a continuous decrease in spine density during disease progression, which we could ascribe to a diminished fraction of gained spines. Remaining spines were enlarged and elongated, thus providing evidence for morphological reorganization in compensation for synaptic dysfunction. Remarkably, loss of dendritic spines in cortical pyramidal neurons occurred in the absence of neurofibrillary tangles (NFTs). Therefore, we consider prefibrillar tau species as causative for the observed impairment in spine plasticity. CONCLUSIONS: Dendritic spine plasticity and morphology are altered in layer V cortical neurons of P301S tau transgenic mice in vivo. This does not coincide with the detection of hyperphosphorylated tau in dendritic spines. |
format | Online Article Text |
id | pubmed-3880070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38800702014-01-04 Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice Hoffmann, Nadine A Dorostkar, Mario M Blumenstock, Sonja Goedert, Michel Herms, Jochen Acta Neuropathol Commun Research BACKGROUND: Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer’s disease (AD), synaptic failure and cognitive decline correlate best with the grade of tau-pathology. To address synaptic alterations in tauopathies, we analyzed the effects of mutant tau expression on excitatory postsynapses in vivo. RESULTS: Here we followed the fate of single dendritic spines in the neocortex of a tauopathy mouse model, expressing human P301S mutated tau, for a period of two weeks. We observed a continuous decrease in spine density during disease progression, which we could ascribe to a diminished fraction of gained spines. Remaining spines were enlarged and elongated, thus providing evidence for morphological reorganization in compensation for synaptic dysfunction. Remarkably, loss of dendritic spines in cortical pyramidal neurons occurred in the absence of neurofibrillary tangles (NFTs). Therefore, we consider prefibrillar tau species as causative for the observed impairment in spine plasticity. CONCLUSIONS: Dendritic spine plasticity and morphology are altered in layer V cortical neurons of P301S tau transgenic mice in vivo. This does not coincide with the detection of hyperphosphorylated tau in dendritic spines. BioMed Central 2013-12-17 /pmc/articles/PMC3880070/ /pubmed/24344647 http://dx.doi.org/10.1186/2051-5960-1-82 Text en Copyright © 2013 Hoffmann et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Hoffmann, Nadine A Dorostkar, Mario M Blumenstock, Sonja Goedert, Michel Herms, Jochen Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice |
title | Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice |
title_full | Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice |
title_fullStr | Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice |
title_full_unstemmed | Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice |
title_short | Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice |
title_sort | impaired plasticity of cortical dendritic spines in p301s tau transgenic mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880070/ https://www.ncbi.nlm.nih.gov/pubmed/24344647 http://dx.doi.org/10.1186/2051-5960-1-82 |
work_keys_str_mv | AT hoffmannnadinea impairedplasticityofcorticaldendriticspinesinp301stautransgenicmice AT dorostkarmariom impairedplasticityofcorticaldendriticspinesinp301stautransgenicmice AT blumenstocksonja impairedplasticityofcorticaldendriticspinesinp301stautransgenicmice AT goedertmichel impairedplasticityofcorticaldendriticspinesinp301stautransgenicmice AT hermsjochen impairedplasticityofcorticaldendriticspinesinp301stautransgenicmice |