Waschek James A, Cohen Joseph R, Chi Gloria C, Proszynski Tomasz J, Niewiadomski Pawel
1 Intellectual Development and Disabilities Research Center, The David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
2 Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
ASN Neuro. 2017 May-Jun;9(3):1759091417708720. doi: 10.1177/1759091417708720.
New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitor cells (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion. Gene array and reconstitution assays indicate that this effect can be attributed to the regulation of ECM components and ECM-modifying enzymes in aNPCs by PACAP. Our work suggests that PACAP regulates a bidirectional interaction between the aNPCs and their niche: PACAP modifies ECM production and remodeling, in turn the ECM regulates progenitor cell adherence. We speculate that PACAP may in this manner help restrict adult neural progenitors to the stem cell niche in vivo, with potential significance for aNPC function in physiological and pathological states.
在哺乳动物的一生中，新的神经元在大脑中被称为神经源性微环境的生发区产生：侧脑室的室下区和海马齿状回的颗粒下区。这些微环境包含一类被称为成年神经祖细胞（aNPCs）的细胞亚群，它们能够自我更新，并产生新的神经元和神经胶质细胞。aNPCs受微环境中多种因素的调控，包括细胞外基质（ECM）。我们发现神经肽垂体腺苷酸环化酶激活肽（PACAP）通过增加其表面黏附力来影响源自室下区的aNPCs。基因阵列和重组实验表明，这种作用可归因于PACAP对aNPCs中ECM成分和ECM修饰酶的调控。我们的研究表明，PACAP调节aNPCs与其微环境之间的双向相互作用：PACAP改变ECM的产生和重塑，反过来ECM调节祖细胞的黏附。我们推测，PACAP可能以这种方式在体内帮助将成年神经祖细胞限制在干细胞微环境中，这对aNPCs在生理和病理状态下的功能具有潜在意义。
