Age-Dependent Neuroplasticity Mechanisms in Alzheimer Tg2576 Mice Following Modulation of Brain Amyloid-β Levels
| Autor: | Carina M. Thomé, Amelia Marutle, Nigel H. Greig, Anna M. Lilja, Elisa Storelli, Christina Unger-Lithner, Agneta Nordberg, Daniel Gonzalez, Jennie Röjdner, Tamanna Mustafiz |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology Mouse Physostigmine Interleukin-1beta lcsh:Medicine neurons Plaque Amyloid Hippocampal formation Hippocampus Biochemistry Mice 0302 clinical medicine Neurobiology of Disease and Regeneration lcsh:Science Neuropathology brain disease 0303 health sciences Multidisciplinary Neuronal Plasticity biology Neurogenesis Age Factors Brain Neurochemistry Animal Models drug therapy Neurology Medicine Female Alzheimer's disease Alzheimer’s disease Research Article Genetically modified mouse medicine.medical_specialty Drugs and Devices Doublecortin Protein Drug Research and Development Mice Transgenic Proinflammatory cytokine 03 medical and health sciences Model Organisms Neuropharmacology Developmental Neuroscience Alzheimer Disease Diagnostic Medicine Internal medicine mental disorders enzyme-linked immunoassays medicine Animals Biology 030304 developmental biology Amyloid beta-Peptides business.industry Tumor Necrosis Factor-alpha Dentate gyrus lcsh:R Proteins medicine.disease hippocampal neurogenesis cytokines Doublecortin Disease Models Animal Endocrinology cell proliferation nervous system Anatomical Pathology Cellular Neuroscience Synapses biology.protein Synaptophysin lcsh:Q Dementia Molecular Neuroscience business 030217 neurology & neurosurgery Developmental Biology Neuroscience Synaptic Plasticity |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 3, p e58752 (2013) |
| Popis: | The objective of this study was to investigate the effects of modulating brain amyloid-b (Ab) levels at different stages ofamyloid pathology on synaptic function, inflammatory cell changes and hippocampal neurogenesis, i.e. processesperturbed in Alzheimer’s disease (AD). Young (4- to 6-month-old) and older (15- to 18-month-old) APPSWE transgenic(Tg2576) mice were treated with the AD candidate drug (+)-phenserine for 16 consecutive days. We found significantreductions in insoluble Ab1-42 levels in the cortices of both young and older transgenic mice, while significant reductions insoluble Ab1-42 levels and insoluble Ab1-40 levels were only found in animals aged 15–18 months. Autoradiography bindingwith the amyloid ligand Pittsburgh Compound B (3H-PIB) revealed a trend for reduced fibrillar Ab deposition in the brains ofolder phenserine-treated Tg2576 mice. Phenserine treatment increased cortical synaptophysin levels in younger mice, whiledecreased interleukin-1b and increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels weredetected in the cortices of older mice. The reduction in Ab1-42 levels was associated with an increased number ofbromodeoxyuridine-positive proliferating cells in the hippocampi of both young and older Tg2576 mice. To determinewhether the increased cell proliferation was accompanied by increased neuronal production, the endogenous earlyneuronal marker doublecortin (DCX) was examined in the dentate gyrus (DG) using immunohistochemical detection.Although no changes in the total number of DCX+-expressing neurons were detected in the DG in Tg2576 mice at eitherage following (+)-phenserine treatment, dendritic arborization was increased in differentiating neurons in young Tg2576mice. Collectively, these findings indicate that reducing Ab1-42 levels in Tg2576 mice at an early pathological stage affectssynaptic function by modulating the maturation and plasticity of newborn neurons in the brain. In contrast, lowering Ablevels in Tg2576 mice when Ab plaque pathology is prominent mainly alters the levels of proinflammatory cytokines andchemokines. |
| Databáze: | OpenAIRE |
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