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Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy

Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in...

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Autores principales: Ferrer, Isidro, Andrés-Benito, Pol, Sala-Jarque, Julia, Gil, Vanessa, del Rio, José Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326954/
https://www.ncbi.nlm.nih.gov/pubmed/32670019
http://dx.doi.org/10.3389/fnmol.2020.00101
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author Ferrer, Isidro
Andrés-Benito, Pol
Sala-Jarque, Julia
Gil, Vanessa
del Rio, José Antonio
author_facet Ferrer, Isidro
Andrés-Benito, Pol
Sala-Jarque, Julia
Gil, Vanessa
del Rio, José Antonio
author_sort Ferrer, Isidro
collection PubMed
description Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in the limbic system. AGD has a characteristic pattern progressively involving the entorhinal cortex, amygdala, hippocampus, dentate gyrus, presubiculum, subiculum, hypothalamic nuclei, temporal cortex, and neocortex and brainstem, thus suggesting that argyrophilic grain pathology is a natural model of tau propagation. One series of WT mice was unilaterally inoculated in the hippocampus with sarkosyl-insoluble and sarkosyl-soluble fractions from “pure” AGD at the age of 3 or 7/12 months and killed 3 or 7 months later. Abnormal hyper-phosphorylated tau deposits were found in ipsilateral hippocampal neurons, grains (dots) in the hippocampus, and threads, dots and coiled bodies in the fimbria, as well as the ipsilateral and contralateral corpus callosum. The extension of lesions was wider in animals surviving 7 months compared with those surviving 3 months. Astrocytic inclusions were not observed at any time. Tau deposits were mainly composed of 4Rtau, but also 3Rtau. For comparative purposes, another series of WT mice was inoculated with sarkosyl-insoluble fractions from primary age-related tauopathy (PART), a pure neuronal neurofibrillary tangle 3Rtau + 4Rtau tauopathy involving the deep temporal cortex and limbic system. Abnormal hyper-phosphorylated tau deposits were found in neurons in the ipsilateral hippocampus, coiled bodies and threads in the fimbria, and the ipsilateral and contralateral corpus callosum, which extended with time along the anterior-posterior axis and distant regions such as hypothalamic nuclei and nuclei of the septum when comparing mice surviving 7 months with mice surviving 3 months. Astrocytic inclusions were not observed. Tau deposits were mainly composed of 4Rtau and 3Rtau. These results show the capacity for seeding and spreading of AGD tau and PART tau in the brain of WT mouse, and suggest that characteristics of host tau, in addition to those of inoculated tau, are key to identifying commonalities and differences between human tauopathies and corresponding murine models.
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spelling pubmed-73269542020-07-14 Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy Ferrer, Isidro Andrés-Benito, Pol Sala-Jarque, Julia Gil, Vanessa del Rio, José Antonio Front Mol Neurosci Neuroscience Argyrophilic grain disease (AGD) is a common 4R-tauopathy, causing or contributing to cognitive impairment in the elderly. AGD is characterized neuropathologically by pre-tangles in neurons, dendritic swellings called grains, threads, thorn-shaped astrocytes, and coiled bodies in oligodendrocytes in the limbic system. AGD has a characteristic pattern progressively involving the entorhinal cortex, amygdala, hippocampus, dentate gyrus, presubiculum, subiculum, hypothalamic nuclei, temporal cortex, and neocortex and brainstem, thus suggesting that argyrophilic grain pathology is a natural model of tau propagation. One series of WT mice was unilaterally inoculated in the hippocampus with sarkosyl-insoluble and sarkosyl-soluble fractions from “pure” AGD at the age of 3 or 7/12 months and killed 3 or 7 months later. Abnormal hyper-phosphorylated tau deposits were found in ipsilateral hippocampal neurons, grains (dots) in the hippocampus, and threads, dots and coiled bodies in the fimbria, as well as the ipsilateral and contralateral corpus callosum. The extension of lesions was wider in animals surviving 7 months compared with those surviving 3 months. Astrocytic inclusions were not observed at any time. Tau deposits were mainly composed of 4Rtau, but also 3Rtau. For comparative purposes, another series of WT mice was inoculated with sarkosyl-insoluble fractions from primary age-related tauopathy (PART), a pure neuronal neurofibrillary tangle 3Rtau + 4Rtau tauopathy involving the deep temporal cortex and limbic system. Abnormal hyper-phosphorylated tau deposits were found in neurons in the ipsilateral hippocampus, coiled bodies and threads in the fimbria, and the ipsilateral and contralateral corpus callosum, which extended with time along the anterior-posterior axis and distant regions such as hypothalamic nuclei and nuclei of the septum when comparing mice surviving 7 months with mice surviving 3 months. Astrocytic inclusions were not observed. Tau deposits were mainly composed of 4Rtau and 3Rtau. These results show the capacity for seeding and spreading of AGD tau and PART tau in the brain of WT mouse, and suggest that characteristics of host tau, in addition to those of inoculated tau, are key to identifying commonalities and differences between human tauopathies and corresponding murine models. Frontiers Media S.A. 2020-06-24 /pmc/articles/PMC7326954/ /pubmed/32670019 http://dx.doi.org/10.3389/fnmol.2020.00101 Text en Copyright © 2020 Ferrer, Andrés-Benito, Sala-Jarque, Gil and del Rio. https://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 or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) 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
Ferrer, Isidro
Andrés-Benito, Pol
Sala-Jarque, Julia
Gil, Vanessa
del Rio, José Antonio
Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy
title Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy
title_full Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy
title_fullStr Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy
title_full_unstemmed Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy
title_short Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons With Primary Age-Related Tauopathy
title_sort capacity for seeding and spreading of argyrophilic grain disease in a wild-type murine model; comparisons with primary age-related tauopathy
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326954/
https://www.ncbi.nlm.nih.gov/pubmed/32670019
http://dx.doi.org/10.3389/fnmol.2020.00101
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