Bhattarai Prabesh, Thomas Alvin Kuriakose, Zhang Yixin, Kizil Caghan
German Centre for Neurodegenerative Diseases (DZNE) Dresden within Helmholtz Association, Dresden, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
Neurogenesis (Austin). 2017 May 2;4(1):e1322666. doi: 10.1080/23262133.2017.1322666. eCollection 2017.
Alzheimer disease is the most prevalent neurodegenerative disease and is associated with aggregation of Amyloid-β42 peptides. In mammals, Amyloid-β42 causes impaired neural stem/progenitor cell (NSPC) proliferation and neurogenesis, which exacerbate with aging. The molecular programs necessary to enhance NSPC proliferation and neurogenesis in our brains to mount successful regeneration are largely unknown. Therefore, to identify the molecular basis of effective brain regeneration, we previously established an Amyloid-β42 model in adult zebrafish that displayed Alzheimer-like phenotypes reminiscent of humans. Interestingly, zebrafish exhibited enhanced NSPC proliferation and neurogenesis after microinjection of Amyloid-β42 peptide. Here, we compare old and young fish to address the effects of aging on regenerative ability after Amyloid-β42 deposition. We found that aging does not affect the rate of NSPC proliferation but reduces the neurogenic response and microglia/macrophage activation after microinjection of Amyloid-β42 in zebrafish, suggesting an important link between aging, neuroinflammation, regenerative neurogenesis and neural stem cell plasticity.
阿尔茨海默病是最常见的神经退行性疾病，与β淀粉样蛋白42肽的聚集有关。在哺乳动物中，β淀粉样蛋白42会导致神经干/祖细胞（NSPC）增殖受损和神经发生受损，且随着年龄增长而加剧。在我们大脑中增强NSPC增殖和神经发生以实现成功再生所必需的分子程序在很大程度上尚不清楚。因此，为了确定有效脑再生的分子基础，我们之前在成年斑马鱼中建立了一个β淀粉样蛋白42模型，该模型表现出类似于人类的阿尔茨海默样表型。有趣的是，斑马鱼在显微注射β淀粉样蛋白42肽后表现出增强的NSPC增殖和神经发生。在此，我们比较老年和幼年斑马鱼，以探讨衰老对β淀粉样蛋白42沉积后再生能力的影响。我们发现，衰老并不影响NSPC的增殖速率，但会降低斑马鱼在显微注射β淀粉样蛋白42后的神经发生反应和小胶质细胞/巨噬细胞激活，这表明衰老、神经炎症、再生性神经发生和神经干细胞可塑性之间存在重要联系。
