Central and Peripheral NPY Age-Related Regulation: A Comparative Analysis in Fish Translational Models

Abstract

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.

The Application of Synthetic Flavors in Zebrafish (Danio rerio) Rearing with Emphasis on Attractive Ones: Effects on Fish Development, Welfare, and Appetite

“…NPY, besides being expressed also in other tissues like spleen, kidney, and smooth muscle [66,67], interacts with a number of different appetite signals such as corticotropin-releasing factor (CRF), cortisol, CART, orexins, and galanin, suggesting that the NPY response is not exclusively dependent from the ghrelin signal [68]. In addition, NPY is involved in several other physiological functions in fish, like circadian rhythmicity, cardiovascular activity, psychomotor activity, and sexual behavior, which could have affected the present results [69][70][71].…”

A Morphological and Ultrastructural Study of the Anterior Digestive Tract of Adult Nile Tilapia Oreochromis niloticus

“…In view of the key role played by fish both in translational research [53,54] and aquaculture, our work may be of interest in different research settings. This preliminary study provides in-depth morphological data of the stomach of Nile tilapia, inspiring us to formulate a functional hypothesis.…”

Zebrafish as an Emerging Model for Sarcopenia: Considerations, Current Insights, and Future Directions

“…It was demonstrated that the short-lived Turquoise Killifish upregulated H3K27 methylation complexes, leading to chromatin hoarding, and downregulated H3K27 acetylation complexes in the aging process [107]. Recently, a comparative study between the short-lived Turquoise Killifish and the longer-lived zebrafish demonstrated an initial central regulation of the NPY neuropeptide in aging models, with peripheral localization being present in both ageing models, elucidating new mechanisms that warrant further study in both fish species [108].…”