A regional and cellular analysis of the early intracellular and extracellular accumulation of Aβ in the brain of 5XFAD mice
| Autor: | Valentina Secco, Eleonora Daini, Antonietta Vilella, Wenjie Liao, Michele Zoli |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse Mice Transgenic Plaque Amyloid Grey matter Biology Transgenic Model White matter Mice 03 medical and health sciences Sex Factors 0302 clinical medicine Alzheimer Disease medicine Extracellular Animals Humans 5XFAD mice Microglial reactivity Cerebral Cortex Amyloid beta-Peptides Microglia General Neuroscience Intracellular Aβ accumulation Alzheimer's disease Amyloid plaque deposition Pathophysiology Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Female 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Neuroscience Letters. 754:135869 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2021.135869 |
| Popis: | Intracellular Aβ (iAβ) expression, extracellular Aβ (eAβ) plaque formation and microglial reactivity are characteristic neuropathological events of Alzheimer's disease (AD) and have been detected in several transgenic mouse models of this disease. In this work we decided to investigate the early (2-7 months of age) development of these phenomena at both regional and cellular levels in 5XFAD mice, a severe transgenic mouse model of AD. We demonstrated that 1) Aβ pathology develops in many but not all brain regions, 2) iAβ is transient and almost always followed by eAβ in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Aβ pathology and in several white matter regions, eAβ plaques can appear where no iAβ-positive structures were detected. We also showed that male and female mice share a similar regional and cellular pattern of Aβ pathology development that is more prominent in females. Early iAβ is associated to the activation of microglia, while subsequent formation of eAβ plaques is associated with markedly increased density of microglial cells that acquire a characteristic clustered phenotype. Present analysis is relevant to set a reference for pathophysiological studies and to define specific targets for the test of therapeutic interventions in this widely used AD transgenic model. |
| Databáze: | OpenAIRE |
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