Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy
Abstract Traumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-02371-3 |
| _version_ | 1818743721657630720 |
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| author | Linn Streubel-Gallasch Marlena Zyśk Chiara Beretta Anna Erlandsson |
| author_facet | Linn Streubel-Gallasch Marlena Zyśk Chiara Beretta Anna Erlandsson |
| author_sort | Linn Streubel-Gallasch |
| collection | DOAJ |
| description | Abstract Traumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the connection between TBI and Alzheimer’s disease in the aged brain and potential exacerbating factors is still evolving. The aim of this study was to investigate cellular injury-induced processes in the presence of amyloid β (Aβ) pathology. For this purpose, a co-culture system of cortical stem-cell derived astrocytes, neurons and oligodendrocytes were exposed to Aβ42 protofibrils prior to a mechanically induced scratch injury. Cellular responses, including neurodegeneration, glial activation and autophagy was assessed by immunoblotting, immunocytochemistry, ELISA and transmission electron microscopy. Our results demonstrate that the combined burden of Aβ exposure and experimental TBI causes a decline in the number of neurons, the differential expression of the key astrocytic markers glial fibrillary acidic protein and S100 calcium-binding protein beta, mitochondrial alterations and prevents the upregulation of autophagy. Our study provides valuable information about the impact of TBI sustained in the presence of Aβ deposits and helps to advance the understanding of geriatric TBI on the cellular level. |
| first_indexed | 2024-12-18T02:32:55Z |
| format | Article |
| id | doaj.art-7852d151364c4a9a8ae497162b6a2cc3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T02:32:55Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7852d151364c4a9a8ae497162b6a2cc32022-12-21T21:23:51ZengNature PortfolioScientific Reports2045-23222021-11-0111111910.1038/s41598-021-02371-3Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagyLinn Streubel-Gallasch0Marlena Zyśk1Chiara Beretta2Anna Erlandsson3Department of Public Health and Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala UniversityDepartment of Public Health and Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala UniversityDepartment of Public Health and Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala UniversityDepartment of Public Health and Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala UniversityAbstract Traumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the connection between TBI and Alzheimer’s disease in the aged brain and potential exacerbating factors is still evolving. The aim of this study was to investigate cellular injury-induced processes in the presence of amyloid β (Aβ) pathology. For this purpose, a co-culture system of cortical stem-cell derived astrocytes, neurons and oligodendrocytes were exposed to Aβ42 protofibrils prior to a mechanically induced scratch injury. Cellular responses, including neurodegeneration, glial activation and autophagy was assessed by immunoblotting, immunocytochemistry, ELISA and transmission electron microscopy. Our results demonstrate that the combined burden of Aβ exposure and experimental TBI causes a decline in the number of neurons, the differential expression of the key astrocytic markers glial fibrillary acidic protein and S100 calcium-binding protein beta, mitochondrial alterations and prevents the upregulation of autophagy. Our study provides valuable information about the impact of TBI sustained in the presence of Aβ deposits and helps to advance the understanding of geriatric TBI on the cellular level.https://doi.org/10.1038/s41598-021-02371-3 |
| spellingShingle | Linn Streubel-Gallasch Marlena Zyśk Chiara Beretta Anna Erlandsson Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy Scientific Reports |
| title | Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy |
| title_full | Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy |
| title_fullStr | Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy |
| title_full_unstemmed | Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy |
| title_short | Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy |
| title_sort | traumatic brain injury in the presence of aβ pathology affects neuronal survival glial activation and autophagy |
| url | https://doi.org/10.1038/s41598-021-02371-3 |
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