期刊
JOURNAL OF NEUROCHEMISTRY
卷 131, 期 6, 页码 848-858出版社
WILEY
DOI: 10.1111/jnc.12813
关键词
diabetes; high fat diet; Parkinson's disease; synuclein; transgenic mice
资金
- German Center for Neurodegenerative Diseases
- Helmholtz Alliance 'Aging Brain'
- Hertie Foundation
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) -synuclein (AS). To study if diet-induced obesity could be an environmental risk factor for PD-related -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 -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 -synucleinopathies. The molecular and cellular mechanisms remain to be further elucidated.
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