Impaired Performance of Female APP/PS1 Mice in the Morris Water Maze Is Coupled with Increased Aβ Accumulation and Microglial Activation
| Autor: | A M Minogue, Marina A. Lynch, Joseph J. Gallagher |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Interleukin-1beta Antigens Differentiation Myelomonocytic Morris water navigation task Enzyme-Linked Immunosorbent Assay Mice Transgenic Brain tissue Insulysin Presenilin Amyloid beta-Protein Precursor Mice Antigens CD Internal medicine Glial Fibrillary Acidic Protein mental disorders Presenilin-1 Reaction Time medicine Insulin-degrading enzyme Amyloid precursor protein Animals Aspartic Acid Endopeptidases Humans RNA Messenger Cognitive decline Maze Learning Neuroinflammation Analysis of Variance Sex Characteristics Amyloid beta-Peptides CD11b Antigen biology Learning Disabilities business.industry Endocrinology Gene Expression Regulation Neurology biology.protein Spatial learning Female Neprilysin Microglia Neurology (clinical) Amyloid Precursor Protein Secretases business Neuroscience |
| Zdroj: | Neurodegenerative Diseases. 11:33-41 |
| ISSN: | 1660-2862 1660-2854 |
| DOI: | 10.1159/000337458 |
| Popis: | Background: Alzheimer’s disease (AD) is characterized by progressive neuronal loss and cognitive decline. Epidemiological studies suggest that the risk of AD is higher in women even when data are adjusted for age. Objective: We set out to compare changes in 9-month-old male and female mice which overexpress amyloid precursor protein (APP) with presenilin (PS1; APP/PS1 mice) and to evaluate whether any changes were coupled with deficits in spatial learning. Methods: APP/PS1 mice were assessed for their ability to learn in the Morris water maze and Aβ burden assessed by Congo Red and Aβ triple ultrasensitive assay. Neuroinflammatory changes were examined in brain tissue along with expression of Aβ-generating and Aβ-degrading enzymes. Results: A deficit in reversal phase learning in the Morris water maze was observed in female mice and was paralleled by evidence of increased accumulation of Aβ, microglial activation and expression of IL-1β. Accumulation of Aβ was coupled with an increase in expression of BACE-1 and a decrease in insulin-degrading enzyme (IDE). Conclusion: The results indicate that the observed impairment in spatial memory in female APP/PS1 mice correlated with increased Aβ burden and the changes in Aβ may have occurred as a result of enhanced BACE-1 and decreased IDE expression. |
| Databáze: | OpenAIRE |
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