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Truncated tau deregulates synaptic markers in rat model for human tauopathy
Synaptic failure and neurofibrillary degeneration are two major neuropathological substrates of cognitive dysfunction in Alzheimer’s disease (AD). Only a few studies have demonstrated a direct relationship between these two AD hallmarks. To investigate tau mediated synaptic injury we used rat model...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337338/ https://www.ncbi.nlm.nih.gov/pubmed/25755633 http://dx.doi.org/10.3389/fncel.2015.00024 |
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author | Jadhav, Santosh Katina, Stanislav Kovac, Andrej Kazmerova, Zuzana Novak, Michal Zilka, Norbert |
author_facet | Jadhav, Santosh Katina, Stanislav Kovac, Andrej Kazmerova, Zuzana Novak, Michal Zilka, Norbert |
author_sort | Jadhav, Santosh |
collection | PubMed |
description | Synaptic failure and neurofibrillary degeneration are two major neuropathological substrates of cognitive dysfunction in Alzheimer’s disease (AD). Only a few studies have demonstrated a direct relationship between these two AD hallmarks. To investigate tau mediated synaptic injury we used rat model of tauopathy that develops extensive neurofibrillary pathology in the cortex. Using fractionation of cortical synapses, we identified an increase in endogenous rat tau isoforms in presynaptic compartment, and their mis-sorting to the postsynaptic density (PSD). Truncated transgenic tau was distributed in both compartments exhibiting specific phospho-pattern that was characteristic for each synaptic compartment. In the presynaptic compartment, truncated tau was associated with impairment of dynamic stability of microtubules which could be responsible for reduction of synaptic vesicles. In the PSD, truncated tau lowered the levels of neurofilaments. Truncated tau also significantly decreased the synaptic levels of Aβ40 but not Aβ42. These data show that truncated tau differentially deregulates synaptic proteome in pre- and postsynaptic compartments. Importantly, we show that alteration of Aβ can arise downstream of truncated tau pathology. |
format | Online Article Text |
id | pubmed-4337338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-43373382015-03-09 Truncated tau deregulates synaptic markers in rat model for human tauopathy Jadhav, Santosh Katina, Stanislav Kovac, Andrej Kazmerova, Zuzana Novak, Michal Zilka, Norbert Front Cell Neurosci Neuroscience Synaptic failure and neurofibrillary degeneration are two major neuropathological substrates of cognitive dysfunction in Alzheimer’s disease (AD). Only a few studies have demonstrated a direct relationship between these two AD hallmarks. To investigate tau mediated synaptic injury we used rat model of tauopathy that develops extensive neurofibrillary pathology in the cortex. Using fractionation of cortical synapses, we identified an increase in endogenous rat tau isoforms in presynaptic compartment, and their mis-sorting to the postsynaptic density (PSD). Truncated transgenic tau was distributed in both compartments exhibiting specific phospho-pattern that was characteristic for each synaptic compartment. In the presynaptic compartment, truncated tau was associated with impairment of dynamic stability of microtubules which could be responsible for reduction of synaptic vesicles. In the PSD, truncated tau lowered the levels of neurofilaments. Truncated tau also significantly decreased the synaptic levels of Aβ40 but not Aβ42. These data show that truncated tau differentially deregulates synaptic proteome in pre- and postsynaptic compartments. Importantly, we show that alteration of Aβ can arise downstream of truncated tau pathology. Frontiers Media S.A. 2015-02-23 /pmc/articles/PMC4337338/ /pubmed/25755633 http://dx.doi.org/10.3389/fncel.2015.00024 Text en Copyright © 2015 Jadhav, Katina, Kovac, Kazmerova, Novak and Zilka. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Jadhav, Santosh Katina, Stanislav Kovac, Andrej Kazmerova, Zuzana Novak, Michal Zilka, Norbert Truncated tau deregulates synaptic markers in rat model for human tauopathy |
title | Truncated tau deregulates synaptic markers in rat model for human tauopathy |
title_full | Truncated tau deregulates synaptic markers in rat model for human tauopathy |
title_fullStr | Truncated tau deregulates synaptic markers in rat model for human tauopathy |
title_full_unstemmed | Truncated tau deregulates synaptic markers in rat model for human tauopathy |
title_short | Truncated tau deregulates synaptic markers in rat model for human tauopathy |
title_sort | truncated tau deregulates synaptic markers in rat model for human tauopathy |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337338/ https://www.ncbi.nlm.nih.gov/pubmed/25755633 http://dx.doi.org/10.3389/fncel.2015.00024 |
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