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000165137 037__ $$aDZNE-2022-01442
000165137 041__ $$aEnglish
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000165137 1001_ $$aKilzheimer, Alexander$$b0
000165137 245__ $$aFailure of diet-induced transcriptional adaptations in alpha-synuclein transgenic mice.
000165137 260__ $$aOxford$$bOxford Univ. Press$$c2023
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000165137 520__ $$a Nutritional influences have been discussed as potential modulators of Parkinson's disease (PD) pathology through various epidemiological and physiological studies. In animal models, a high-fat diet (HFD) with greater intake of lipid-derived calories leads to accelerated disease onset and progression. The underlying molecular mechanisms of HFD-induced aggravated pathology, however, remain largely unclear. In this study, we aimed to further illuminate the effects of a fat-enriched diet in PD by examining the brainstem and hippocampal transcriptome of alpha-synuclein transgenic mice exposed to a life-long HFD. Investigating individual transcript isoforms, differential gene expression and co-expression clusters, we observed that transcriptional differences between wild-type (WT) and transgenic animals intensified in both regions under HFD. Both brainstem and hippocampus displayed strikingly similar transcriptomic perturbation patterns. Interestingly, expression differences resulted mainly from responses in WT animals to HFD, while these genes remained largely unchanged or were even slightly oppositely regulated by diet in transgenic animals. Genes and co-expressed gene groups exhibiting this dysregulation were linked to metabolic and mitochondrial pathways. Our findings propose the failure of metabolic adaptions as the potential explanation for accelerated disease unfolding under exposure to HFD. From the identified clusters of co-expressed genes, several candidates lend themselves to further functional investigations.
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000165137 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000165137 650_2 $$2MeSH$$aMice
000165137 650_2 $$2MeSH$$aAnimals
000165137 650_2 $$2MeSH$$aMice, Transgenic
000165137 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000165137 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000165137 650_2 $$2MeSH$$aParkinson Disease: genetics
000165137 650_2 $$2MeSH$$aParkinson Disease: metabolism
000165137 650_2 $$2MeSH$$aDiet, High-Fat: adverse effects
000165137 650_2 $$2MeSH$$aGene Expression Profiling
000165137 650_2 $$2MeSH$$aMice, Inbred C57BL
000165137 7001_ $$aHentrich, Thomas$$b1
000165137 7001_ $$0P:(DE-2719)2630394$$aRotermund, Carola$$b2$$udzne
000165137 7001_ $$0P:(DE-2719)2810803$$aKahle, Philipp J$$b3$$udzne
000165137 7001_ $$00000-0002-9242-2096$$aSchulze-Hentrich, Julia M$$b4
000165137 773__ $$0PERI:(DE-600)1474816-2$$a10.1093/hmg/ddac205$$gp. ddac205$$n3$$p450 - 461$$tHuman molecular genetics$$v32$$x0964-6906$$y2023
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