Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neurogenesis in the aged brain. The chemokine Cxcl13 was found to be upregulated in the brain during aging. Loss of its receptor, Cxcr5, led to increased proliferation and decreased numbers of neuroblasts in the aged subventricular zone (SVZ), together with accumulation of neuroblasts in the rostral migratory stream and olfactory bulb (OB), without increasing the amount of new mature neurons in the OB. The effect on proliferation and migration was specific to neuroblasts and likely mediated through increased levels of systemic IL‐6 and local Cxcl12 expression in the SVZ. Our study raises the possibility of a new mechanism by which interplay between systemic and local alterations in inflammation regulates neurogenesis during aging.

中文翻译：

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Cxcr5 的缺失改变了老年大脑中的神经母细胞增殖和迁移

神经发生，即从神经干细胞产生新神经元，在衰老过程中急剧减少，伴随着全身和大脑炎症的增加。然而，炎症的确切作用以及局部或全身因素是否会导致衰老过程中的神经源性下降尚不清楚。在这里，我们将 CXCR5/5/CXCL13 信号确定为老年大脑神经发生的新调节器。发现趋化因子 Cxcl13 在衰老过程中在大脑中上调。其受体 Cxcr5 的缺失导致衰老脑室下区 (SVZ) 中神经母细胞的增殖增加和数量减少，同时神经母细胞在嘴侧迁移流和嗅球 (OB) 中积累，但不会增加新成熟神经元的数量在 OB 中。对增殖和迁移的影响是特定于成神经细胞的，可能是通过 SVZ 中系统性 IL-6 和局部 Cxcl12 表达水平的增加来介导的。我们的研究提出了一种新机制的可能性，通过该机制，炎症的全身性和局部性改变之间的相互作用调节衰老过程中的神经发生。