Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease
Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting over 10% of the elderly population. Epidemiological evidence indicates that traumatic brain injury (TBI) is an important risk factor for developing AD later in life. However, which injury-induced processes that contr...
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Uppsala universitet, Geriatrik
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ftuppsalauniv:oai:DiVA.org:uu-400408 2023-05-15T15:13:34+02:00 Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease Zysk, Marlena Clausen, Fredrik Aguilar, Ximena Sehlin, Dag Syvänen, Stina Erlandsson, Anna 2019 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-400408 https://doi.org/10.3233/JAD-190572 eng eng Uppsala universitet, Geriatrik Uppsala universitet, Enblad: Neurokirurgi IOS PRESS Journal of Alzheimer's Disease, 1387-2877, 2019, 72:1, s. 161-180 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-400408 doi:10.3233/JAD-190572 PMID 31561367 ISI:000500780700014 info:eu-repo/semantics/openAccess Alzheimer's disease amyloid-beta inflammation Morris water maze neurodegeneration astrocytes PET traumatic brain injury Neurology Neurologi Article in journal info:eu-repo/semantics/article text 2019 ftuppsalauniv https://doi.org/10.3233/JAD-190572 2023-02-23T21:51:22Z Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting over 10% of the elderly population. Epidemiological evidence indicates that traumatic brain injury (TBI) is an important risk factor for developing AD later in life. However, which injury-induced processes that contribute to the disease onset remains unclear. The aim with the present study was to identify cellular processes that could link TBI to AD development, by investigating the chronic impact of two different injury models, controlled cortical impact (CCI) and midline fluid percussion injury (mFPI). The trauma was induced in 3-month-old tg-ArcSwe mice, carrying the Arctic mutation along with the Swedish mutation, and the influence of TBI on AD progression was analyzed at 12- and 24-weeks post-injury. The long-term effect of the TBI on memory deficiency, amyloid-beta (A beta) pathology, neurodegeneration and inflammation was investigated by Morris water maze, PET imaging, immunohistochemistry, and biochemical analyses. Morris water maze analysis demonstrated that mice subjected to CCI or mFPI performed significantly worse than uninjured tg-ArcSwe mice, especially at the later time point. Moreover, the injured mice showed a late upregulation of reactive gliosis, which concurred with a more pronounced A beta pathology, compared to uninjured AD mice. Our results suggest that the delayed glial activation following TBI may be an important link between the two diseases. However, further studies in both experimental models and human TBI patients will be required to fully elucidate the reasons why TBI increases the risk of neurodegeneration. Article in Journal/Newspaper Arctic Uppsala University: Publications (DiVA) Arctic Journal of Alzheimer's Disease 72 1 161 180 |
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Uppsala University: Publications (DiVA) |
op_collection_id |
ftuppsalauniv |
language |
English |
topic |
Alzheimer's disease amyloid-beta inflammation Morris water maze neurodegeneration astrocytes PET traumatic brain injury Neurology Neurologi |
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Alzheimer's disease amyloid-beta inflammation Morris water maze neurodegeneration astrocytes PET traumatic brain injury Neurology Neurologi Zysk, Marlena Clausen, Fredrik Aguilar, Ximena Sehlin, Dag Syvänen, Stina Erlandsson, Anna Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease |
topic_facet |
Alzheimer's disease amyloid-beta inflammation Morris water maze neurodegeneration astrocytes PET traumatic brain injury Neurology Neurologi |
description |
Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting over 10% of the elderly population. Epidemiological evidence indicates that traumatic brain injury (TBI) is an important risk factor for developing AD later in life. However, which injury-induced processes that contribute to the disease onset remains unclear. The aim with the present study was to identify cellular processes that could link TBI to AD development, by investigating the chronic impact of two different injury models, controlled cortical impact (CCI) and midline fluid percussion injury (mFPI). The trauma was induced in 3-month-old tg-ArcSwe mice, carrying the Arctic mutation along with the Swedish mutation, and the influence of TBI on AD progression was analyzed at 12- and 24-weeks post-injury. The long-term effect of the TBI on memory deficiency, amyloid-beta (A beta) pathology, neurodegeneration and inflammation was investigated by Morris water maze, PET imaging, immunohistochemistry, and biochemical analyses. Morris water maze analysis demonstrated that mice subjected to CCI or mFPI performed significantly worse than uninjured tg-ArcSwe mice, especially at the later time point. Moreover, the injured mice showed a late upregulation of reactive gliosis, which concurred with a more pronounced A beta pathology, compared to uninjured AD mice. Our results suggest that the delayed glial activation following TBI may be an important link between the two diseases. However, further studies in both experimental models and human TBI patients will be required to fully elucidate the reasons why TBI increases the risk of neurodegeneration. |
format |
Article in Journal/Newspaper |
author |
Zysk, Marlena Clausen, Fredrik Aguilar, Ximena Sehlin, Dag Syvänen, Stina Erlandsson, Anna |
author_facet |
Zysk, Marlena Clausen, Fredrik Aguilar, Ximena Sehlin, Dag Syvänen, Stina Erlandsson, Anna |
author_sort |
Zysk, Marlena |
title |
Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease |
title_short |
Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease |
title_full |
Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease |
title_fullStr |
Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease |
title_full_unstemmed |
Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease |
title_sort |
long-term effects of traumatic brain injury in a mouse model of alzheimer's disease |
publisher |
Uppsala universitet, Geriatrik |
publishDate |
2019 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-400408 https://doi.org/10.3233/JAD-190572 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_relation |
Journal of Alzheimer's Disease, 1387-2877, 2019, 72:1, s. 161-180 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-400408 doi:10.3233/JAD-190572 PMID 31561367 ISI:000500780700014 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.3233/JAD-190572 |
container_title |
Journal of Alzheimer's Disease |
container_volume |
72 |
container_issue |
1 |
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161 |
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180 |
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1766344104283734016 |