Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
Glia. 2012 May;60(5):751-60. doi: 10.1002/glia.22305. Epub 2012 Feb 15.
Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies.
中枢神经系统和周围神经系统都容易出现多种与年龄相关的神经功能缺陷，这些缺陷通常归因于少突胶质细胞功能的未知改变。为了揭示衰老对神经胶质细胞中受影响的生物学过程，我们分析了富含施万细胞的小鼠坐骨神经在整个生命周期中的 17 个时间点（从出生到衰老）的基因表达。通过将这些数据与携带 Pmp22、SCAP 或 Lpin1 缺失的髓鞘小鼠突变体的基因表达数据相结合，我们发现大多数与年龄相关的转录本也受髓鞘突变体的影响（54.4%），并在周围神经系统发育过程中受到调控（59.5%），这表明受影响的分子途径具有高度的重叠性。衰老过程中的表达谱复制了在神经病变模型中观察到的转录变化方向；然而，与周围神经系统发育相比，它们的方向相反。衰老过程中变化最显著的生物学过程涉及炎症/免疫反应和脂质代谢。有趣的是，这两条途径在衰老的视神经中都有类似的变化，这表明在富含神经胶质细胞的中枢和周围神经系统衰老过程中，类似的生物学过程受到影响。我们对三种不同生物学条件（包括发育、衰老和髓鞘疾病）中的基因表达进行的综合比较，揭示了它们之间以前未预料到的关系，并确定了脂质代谢和炎症/免疫反应途径作为预防或延迟目前无法治愈的与年龄相关的和遗传性神经病变的潜在治疗靶点。
