Diet-induced obesity accelerates the onset of terminal phenotypes in α-synuclein transgenic mice
| Autor: | Felicia M. Truckenmüller, Philipp J. Kahle, Carola Rotermund, Heinrich Schell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Transgene metabolism [Parkinson Disease] Mice Transgenic Biology Biochemistry Article Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine metabolism [Obesity] medicine Animals Obesity ddc:610 metabolism [alpha-Synuclein] Neuroinflammation Alpha-synuclein Neurons Neurodegeneration Dystrophy Brain Parkinson Disease Snca protein mouse medicine.disease Animal Feed Astrogliosis Mice Inbred C57BL Disease Models Animal Endocrinology Phenotype chemistry metabolism [Brain] metabolism [Neurons] Synuclein alpha-Synuclein |
| Zdroj: | Journal of neurochemistry 131(6), 848-858 (2014). doi:10.1111/jnc.12813 |
| DOI: | 10.1111/jnc.12813 |
| Popis: | Parkinson's disease (PD) and diabetes belong to the most common neurodegenerative and metabolic syndromes, respectively. Epidemiological links between these two frequent disorders are controversial. The neuropathological hallmarks of PD are protein aggregates composed of amyloid-like fibrillar and serine-129 phosphorylated (pS129) α-synuclein (AS). To study if diet-induced obesity could be an environmental risk factor for PD-related α-synucleinopathy, transgenic (TG) mice, expressing the human mutant A30P AS in brain neurons, were subjected after weaning to a lifelong high fat diet (HFD). The TG mice became obese and glucose-intolerant, as did the wild-type controls. Upon aging, HFD significantly accelerated the onset of the lethal locomotor phenotype. Coinciding with the premature movement phenotype and death, HFD accelerated the age of onset of brainstem α-synucleinopathy as detected by immunostaining with antibodies against pathology-associated pS129. Amyloid-like neuropathology was confirmed by thioflavin S staining. Accelerated onset of neurodegeneration was indicated by Gallyas silver-positive neuronal dystrophy as well as astrogliosis. Phosphorylation of the activation sites of the pro-survival signaling intermediate Akt was reduced in younger TG mice after HFD. Thus, diet-induced obesity may be an environmental risk factor for the development of α-synucleinopathies. The molecular and cellular mechanisms remain to be further elucidated. Life-long high fat diet (HFD) induces obesity and glucose intolerance in a transgenic mouse model for α-synucleinopathy and thereby leads to decreased life span as well as accelerated age of onset of the terminal phenotype. This is accompanied by increased neuroinflammation and premature α-synuclein pathology in the brainstems of the HFD-fed mice. |
| Databáze: | OpenAIRE |
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