Department Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy.
Int J Mol Sci. 2022 Mar 30;23(7):3839. doi: 10.3390/ijms23073839.
NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age-related regulation of NPY in the brain and foregut of the shortest- and longest-lived fish species, Nothobranchius furzeri and Danio rerio, respectively. These two research models, despite some similarities, display profound biological differences making them attractive vertebrates to elucidate the mechanisms underlying the regulation of neuropeptide synthesis and function. It is noteworthy that in both fish species only Npya has been identified, while in the other teleosts two classes of NPY (Npya and Npyb) have been annotated. Our findings document that in both species: (i) NPY is centrally regulated; (ii) NPY levels increase in the brain during aging; (iii) NPY is localized in the enteroendocrine cells as well as in the myenteric plexus and drastically decreases in old animals. According to our data, the age-related regulation in the gut resembles that described in other vertebrate species while the increased levels in the brain offer the unique possibility to explore the role of NPY in model organisms to develop future experimental and translatable approaches.
NPY 是脊椎动物脑中含量最丰富的神经肽之一，主要参与食物摄入的调节。NPY 系统也与衰老过程有关，通过自噬调节对神经元存活有有益影响。在这里，我们分别研究了寿命最短和最长的鱼类，即非洲鲫鱼和斑马鱼的脑中及前肠的 NPY 相关的年龄调节。这两个研究模型虽然存在一些相似之处，但表现出了深刻的生物学差异，使它们成为阐明神经肽合成和功能调节机制的有吸引力的脊椎动物。值得注意的是，在这两种鱼类中，仅鉴定出了 Npya，而在其他硬骨鱼类中则注释了两类 NPY（Npya 和 Npyb）。我们的研究结果表明，在这两种鱼类中：（i）NPY 受中枢调控；（ii）随着年龄的增长，NPY 水平在脑中增加；（iii）NPY 定位于肠内分泌细胞以及肌间神经丛，并在老年动物中急剧减少。根据我们的数据，肠道中的年龄相关调节类似于在其他脊椎动物中描述的调节，而脑中水平的升高为探索 NPY 在模式生物中的作用提供了独特的可能性，以开发未来的实验和可转化的方法。
