Characterization of Impaired Cerebrovascular Structure in APP/PS1 Mouse Brains
Autor: | Gary L. Dunbar, Kee Chan Ahn, Panchanan Maiti, Hyeon Cheol Cha, Won Cheoul Jang, Cameron Learman, Mee Sook Song |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Genetically modified mouse Pathology medicine.medical_specialty Mice Transgenic Plaque Amyloid Blood–brain barrier Amyloid beta-Protein Precursor Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Presenilin-1 medicine Amyloid precursor protein Animals Senile plaques biology business.industry General Neuroscience Neurodegeneration Glucose transporter Brain medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier Astrocytes Nerve Degeneration biology.protein GLUT1 Tauopathy business 030217 neurology & neurosurgery |
Zdroj: | Neuroscience. 385:246-254 |
ISSN: | 0306-4522 |
Popis: | Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood-brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD. We previously reported that astrocytes, essential components of BBB, were chronically activated and some deteriorated in the brain of 5xFAD, an amyloid precursor protein/presenilin1 (APP/PS1) transgenic mouse model. Thus, it is rational to investigate if any vascular dysfunction is associated with considerable activation of astrocytes in APP/PS1 mouse model. In this study, we observed that cerebrovascular pathology was associated with large scale of reactive astrocytes and neurodegeneration in an Aβ plague-generating mouse model. Using 5xFAD mouse brains, we demonstrate damaged brain vessels and reduced expression of glucose transporter 1 (GLUT1), the main glucose transporter, and a tight junction protein zonula occludens-1 (ZO-1) of cerebrovascular endothelial cells. This vascular pathology was closely associated with astrocytic deterioration and neuronal loss due to buildup of Aβ plaques in 5xFAD mouse brains. |
Databáze: | OpenAIRE |
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