Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
PLoS One. 2013 Apr 30;8(4):e62456. doi: 10.1371/journal.pone.0062456. Print 2013.
Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease (PD). Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, we show early signs of aging in SNpc, which are more evident than in ventral tegmental area (VTA), a region adjacent to SNpc but less affected in PD. Aging-associated early changes in transcriptome were investigated comparing late middle-aged (18 months old) to young (2 months old) mice in both SNpc and VTA. A meta-analysis of published microarray studies allowed us to generate a common "transcriptional signature" of the aged (≥ 24 months old) mouse brain. SNpc of late-middle aged mice shared characteristics with the transcriptional signature, suggesting an accelerated aging in SNpc. Age-dependent changes in gene expression specific to SNpc were also observed, which were related to neuronal functions and inflammation. Future studies could greatly help determine the contribution of these changes to SNpc aging. These data help understand the processes underlying SNpc aging and their potential contribution to age-related disorders like PD.
黑质致密部（SNpc）对正常衰老高度敏感，并且在帕金森病（PD）中选择性退化。到目前为止，使用高通量技术尚未充分研究 SNpc 衰老背后的分子机制。在这里，我们展示了 SNpc 衰老的早期迹象，这些迹象比毗邻 SNpc 的腹侧被盖区（VTA）更为明显，但在 PD 中受影响较小。通过比较 SNpc 和 VTA 中晚期中年（18 个月龄）和年轻（2 个月龄）小鼠，研究了转录组中的与衰老相关的早期变化。对已发表的微阵列研究进行荟萃分析，使我们能够生成老年（≥24 个月龄）小鼠大脑的通用“转录特征”。晚期中年小鼠的 SNpc 与转录特征具有相似特征，表明 SNpc 加速衰老。还观察到与神经元功能和炎症相关的 SNpc 特异性的年龄相关基因表达变化。未来的研究可以极大地帮助确定这些变化对 SNpc 衰老的贡献。这些数据有助于了解 SNpc 衰老背后的过程及其对 PD 等与年龄相关的疾病的潜在贡献。
