Failure of diet-induced transcriptional adaptations in alpha-synuclein transgenic mice
| العنوان: | Failure of diet-induced transcriptional adaptations in alpha-synuclein transgenic mice |
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| المؤلفون: | Alexander Kilzheimer, Thomas Hentrich, Carola Rotermund, Philipp J Kahle, Julia M Schulze-Hentrich |
| المصدر: | Human molecular genetics 32(3), 450-461 (2023). doi:10.1093/hmg/ddac205 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Gene Expression Profiling, metabolism [Parkinson Disease], Mice, Transgenic, General Medicine, Mice, Inbred C57BL, Mice, genetics [Parkinson Disease], ddc:570, genetics [alpha-Synuclein], alpha-Synuclein, Genetics, Animals, metabolism [alpha-Synuclein], adverse effects [Diet, High-Fat], Molecular Biology, Genetics (clinical) |
| الوصف: | Nutritional influences have been discussed as potential modulators of Parkinson’s disease (PD) pathology through various epidemiological and physiological studies. In animal models, a high-fat diet (HFD) with greater intake of lipid-derived calories leads to accelerated disease onset and progression. The underlying molecular mechanisms of HFD-induced aggravated pathology, however, remain largely unclear. In this study, we aimed to further illuminate the effects of a fat-enriched diet in PD by examining the brainstem and hippocampal transcriptome of alpha-synuclein transgenic mice exposed to a life-long HFD. Investigating individual transcript isoforms, differential gene expression and co-expression clusters, we observed that transcriptional differences between wild-type (WT) and transgenic animals intensified in both regions under HFD. Both brainstem and hippocampus displayed strikingly similar transcriptomic perturbation patterns. Interestingly, expression differences resulted mainly from responses in WT animals to HFD, while these genes remained largely unchanged or were even slightly oppositely regulated by diet in transgenic animals. Genes and co-expressed gene groups exhibiting this dysregulation were linked to metabolic and mitochondrial pathways. Our findings propose the failure of metabolic adaptions as the potential explanation for accelerated disease unfolding under exposure to HFD. From the identified clusters of co-expressed genes, several candidates lend themselves to further functional investigations. |
| تدمد: | 1460-2083 0964-6906 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea1796898c93b59fc865d9cb30511ebb https://doi.org/10.1093/hmg/ddac205 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ea1796898c93b59fc865d9cb30511ebb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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