Table_4_Gene expression changes in cerebellum induced by dietary restriction.XLSX

BackgroundDietary restriction (DR) is a well-established universal anti-aging intervention, and is neuroprotective in multiple models of nervous system disease, including models with cerebellar pathology. The beneficial effects of DR are associated with a rearrangement of gene expression that modulate metabolic and cytoprotective pathways. However, the effect of DR on the cerebellar transcriptome remained to be fully defined.ResultsHere we analyzed the effect of a classical 30% DR protocol on the transcriptome of cerebellar cortex of young-adult male mice using RNAseq. We found that about 5% of expressed genes were differentially expressed in DR cerebellum, the far majority of whom showing subtle expression changes. A large proportion of down-regulated genes are implicated in signaling pathways, in particular pathways associated with neuronal signaling. DR up regulated pathways in large part were associated with cytoprotection and DNA repair. Analysis of the expression of cell-specific gene sets, indicated a strong enrichment of DR down genes in Purkinje cells, while genes specifically associated with granule cells did not show such a preferential down-regulation.ConclusionOur data show that DR may have a clear effect on the cerebellar transcriptome inducing a mild shift from physiology towards maintenance and repair, and having cell-type specific effects.

背景：饮食限制（DR）是一种已广泛认可的普遍抗衰老干预措施，并在多种神经系统疾病模型中表现出神经保护作用，包括具有小脑病理学的模型。DR的有益效应与调节代谢和细胞保护途径的基因表达的重排相关。然而，DR对小脑转录组的影响尚未得到全面定义。结果：在本研究中，我们利用RNAseq技术分析了经典30%DR方案对年轻成年雄性小鼠小脑皮层转录组的影响。我们发现，约5%的表达基因在DR小脑中表现出差异表达，其中绝大多数表现出微妙的表达变化。大量下调的基因与信号通路相关，尤其是与神经元信号相关的通路。DR上调的通路在很大程度上与细胞保护及DNA修复相关。对细胞特异性基因集的表达分析表明，DR下调基因在浦肯野细胞中富集程度较高，而与颗粒细胞特异性相关的基因并未表现出这种偏好性下调。结论：我们的数据显示，DR可能对小脑转录组产生明显影响，诱导生理状态向维持与修复方向的轻微转变，并具有细胞类型特异性效应。