| Autor: |
Dhwani S. Korde, Christian Humpel |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Biomolecules, Vol 12, Iss 9, p 1164 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2218-273X |
| DOI: |
10.3390/biom12091164 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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