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Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures
Tau pathology extends throughout the brain in a prion-like fashion through connected brain regions. However, the details of the underlying mechanisms are incompletely understood. The present study aims to examine the spreading of P301S aggregated tau, a mutation that is implicated in tauopathies, us...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496515/ https://www.ncbi.nlm.nih.gov/pubmed/36139003 http://dx.doi.org/10.3390/biom12091164 |
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author | Korde, Dhwani S. Humpel, Christian |
author_facet | Korde, Dhwani S. Humpel, Christian |
author_sort | Korde, Dhwani S. |
collection | PubMed |
description | Tau pathology extends throughout the brain in a prion-like fashion through connected brain regions. However, the details of the underlying mechanisms are incompletely understood. The present study aims to examine the spreading of P301S aggregated tau, a mutation that is implicated in tauopathies, using organotypic slice cultures. Coronal hippocampal organotypic brain slices (170 µm) were prepared from postnatal (day 8–10) C57BL6 wild-type mice. Collagen hydrogels loaded with P301S aggregated tau were applied to slices and the spread of tau was assessed by immunohistochemistry after 8 weeks in culture. Collagen hydrogels prove to be an effective protein delivery system subject to natural degradation in 14 days and they release tau proteins up to 8 weeks. Slices with un- and hyperphosphorylated P301S aggregated tau demonstrate significant spreading to the ventral parts of the hippocampal slices compared to empty collagen hydrogels after 8 weeks. Moreover, the spread of P301S aggregated tau occurs in a time-dependent manner, which was interrupted when the neuroanatomical pathways are lesioned. We illustrate that the spreading of tau can be investigated in organotypic slice cultures using collagen hydrogels to achieve a localized application and slow release of tau proteins. P301S aggregated tau significantly spreads to the ventral areas of the slices, suggesting that the disease-relevant aggregated tau form possesses spreading potential. Thus, the results offer a novel experimental approach to investigate tau pathology. |
format | Online Article Text |
id | pubmed-9496515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94965152022-09-23 Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures Korde, Dhwani S. Humpel, Christian Biomolecules Article Tau pathology extends throughout the brain in a prion-like fashion through connected brain regions. However, the details of the underlying mechanisms are incompletely understood. The present study aims to examine the spreading of P301S aggregated tau, a mutation that is implicated in tauopathies, using organotypic slice cultures. Coronal hippocampal organotypic brain slices (170 µm) were prepared from postnatal (day 8–10) C57BL6 wild-type mice. Collagen hydrogels loaded with P301S aggregated tau were applied to slices and the spread of tau was assessed by immunohistochemistry after 8 weeks in culture. Collagen hydrogels prove to be an effective protein delivery system subject to natural degradation in 14 days and they release tau proteins up to 8 weeks. Slices with un- and hyperphosphorylated P301S aggregated tau demonstrate significant spreading to the ventral parts of the hippocampal slices compared to empty collagen hydrogels after 8 weeks. Moreover, the spread of P301S aggregated tau occurs in a time-dependent manner, which was interrupted when the neuroanatomical pathways are lesioned. We illustrate that the spreading of tau can be investigated in organotypic slice cultures using collagen hydrogels to achieve a localized application and slow release of tau proteins. P301S aggregated tau significantly spreads to the ventral areas of the slices, suggesting that the disease-relevant aggregated tau form possesses spreading potential. Thus, the results offer a novel experimental approach to investigate tau pathology. MDPI 2022-08-23 /pmc/articles/PMC9496515/ /pubmed/36139003 http://dx.doi.org/10.3390/biom12091164 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Korde, Dhwani S. Humpel, Christian Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures |
title | Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures |
title_full | Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures |
title_fullStr | Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures |
title_full_unstemmed | Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures |
title_short | Spreading of P301S Aggregated Tau Investigated in Organotypic Mouse Brain Slice Cultures |
title_sort | spreading of p301s aggregated tau investigated in organotypic mouse brain slice cultures |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496515/ https://www.ncbi.nlm.nih.gov/pubmed/36139003 http://dx.doi.org/10.3390/biom12091164 |
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