Diet-induced insulin resistance elevates hippocampal glutamate as well as VGLUT1 and GFAP expression in AβPP/PS1 mice
| Autor: | Andrzej Bartke, Yimin Fang, Erin R. Hascup, Heather A. Boger, Kevin N. Hascup, Mary K. Russell, Sarah O. Broderick |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Amyloid beta Vesicular glutamate transporter 1 Excitotoxicity Glutamic Acid Mice Transgenic Hippocampal formation Diet High-Fat medicine.disease_cause Hippocampus Biochemistry Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Insulin resistance Alzheimer Disease Internal medicine Glial Fibrillary Acidic Protein medicine Hyperinsulinemia Animals biology business.industry Glutamate receptor medicine.disease Astrogliosis Mice Inbred C57BL 030104 developmental biology Endocrinology Vesicular Glutamate Transport Protein 1 biology.protein Insulin Resistance business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurochemistry. 148:219-237 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/jnc.14634 |
| Popis: | The symptomologies of Alzheimer's disease (AD) develop over decades suggesting modifiable lifestyle factors may contribute to disease pathogenesis. In humans, hyperinsulinemia associated with type 2 diabetes mellitus increases the risk for developing AD and both diseases share similar age-related etiologies including amyloidogenesis. Since we have demonstrated that soluble Aβ42 elicits glutamate release, we wanted to understand how diet-induced insulin resistance alters hippocampal glutamate dynamics, which are important for memory formation and consolidation. Eight to twelve-week-old C57BL/6J and AβPP/PS1 mice were placed on either a low-fat diet or high-fat diet (HFD) for 8 months. A HFD led to significant weight increases as well as impaired insulin sensitivity, glucose tolerance, and learning in both C57BL/6J and AβPP/PS1 mice. AβPP/PS1 low-fat diet mice had elevated hippocampal basal as well as stimulus-evoked glutamate release that was further increased with consumption of a HFD. Immunohistochemistry indicated an increase in vesicular glutamate transporter 1 and glial fibrillary acidic protein density in hippocampal subregions corresponding with this elevated extracellular glutamate. While no differences in hippocampal plaque load were observed, the elevated astrogliotic response surrounding the plaques in AβPP/PS1 HFD mice may have been a compensatory mechanism to control plaque accumulation. These data support that AβPP/PS1 mice have chronically elevated extracellular glutamate that is exacerbated by a HFD and that modifiable lifestyle factors such as obesity-induced insulin resistance can contribute to AD pathogenesis. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* and for *Open Data* because it made the data publicly available. The data can be accessed at https://osf.io/5whvu (figures for data) and https://osf.io/gd5vf (materials and methods). The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14490. |
| Databáze: | OpenAIRE |
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