The Ames dwarf mutation attenuates Alzheimer's disease phenotype of APP/PS1 mice
| Autor: | Holly M. Brown-Borg, Colin K. Combs, Kendra L. Puig, Whitney Franklin, Joshua A. Kulas, Giulio Taglialatela, Sharlene G. Rakoczy |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Aging medicine.medical_specialty Amyloid beta Gene Expression Thyrotropin Mice Transgenic Plaque Amyloid Article Presenilin Proinflammatory cytokine Amyloid beta-Protein Precursor 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Internal medicine mental disorders Presenilin-1 medicine Amyloid precursor protein Animals Gliosis Insulin-Like Growth Factor I Cells Cultured Homeodomain Proteins biology General Neuroscience Brain medicine.disease Prolactin nervous system diseases Astrogliosis Mice Inbred C57BL Phenotype 030104 developmental biology Endocrinology Growth Hormone Mutation Immunology biology.protein Cytokines Neurology (clinical) Geriatrics and Gerontology Alzheimer's disease medicine.symptom 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of Aging. 40:22-40 |
| ISSN: | 0197-4580 |
| Popis: | APP/PS1 double transgenic mice expressing human mutant amyloid precursor protein (APP) and presenilin-1 (PS-1) demonstrate robust brain Aβ peptide containing plaque deposition, increased markers of oxidative stress, behavioral dysfunction, and proinflammatory gliosis. On the other hand, lack of growth hormone, prolactin, and thyroid-stimulating hormone due to a recessive mutation in the Prop 1 gene (Prop1df) in Ames dwarf mice results in a phenotype characterized by potentiated anti-oxidant mechanisms, improved learning and memory, and significantly increased longevity in homozygous mice. Based upon this, we hypothesized that a similar hormone deficiency might attenuate disease changes in the brains of APP/PS1 mice. To test this idea, APP/PS1 mice were crossed to the Ames dwarf mouse line. APP/PS1, wild type, df/+, df/df, df/+/APP/PS1, and df/df/APP/PS1 mice were compared at 6 months of age through behavioral testing and assessing amyloid burden, reactive gliosis, and brain cytokine levels. df/df mice demonstrated lower brain growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations. This correlated with decreased astrogliosis and microgliosis in the df/df/APP/PS1 mice and, surprisingly, reduced Aβ plaque deposition and Aβ 1-40 and Aβ 1-42 concentrations. The df/df/APP/PS1 mice also demonstrated significantly elevated brain levels of multiple cytokines in spite of the attenuated gliosis. These data indicate that the df/df/APP/PS1 line is a unique resource in which to study aging and resistance to disease and suggest that the affected pituitary hormones may have a role in regulating disease progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect