Ontogenetic Pattern Changes of Nucleobindin-2/Nesfatin-1 in the Brain and Intestinal Bulb of the Short Lived African Turquoise Killifish

Abstract

Nesfatin-1 (Nesf-1) was identified as an anorexigenic and well conserved molecule in rodents and fish. While tissue distribution of NUCB2 (Nucleobindin 2)/Nesf-1 is discretely known in vertebrates, reports on ontogenetic expression are scarce. Here, we examine the age-related central and peripheral expression of NUCB2/Nesf-1 in the teleost African turquoise killifish Nothobranchius furzeri, a consolidated model organism for aging research. We focused our analysis on brain areas responsible for the regulation of food intake and the rostral intestinal bulb, which is analogous of the mammalian stomach. We hypothesize that in our model, the stomach equivalent structure is the main source of NUCB2 mRNA, displaying higher expression levels than those observed in the brain, mainly during aging. Remarkably, its expression significantly increased in the rostral intestinal bulb compared to the brain, which is likely due to the typical anorexia of aging. When analyzing the pattern of expression, we confirmed the distribution in diencephalic areas involved in food intake regulation at all age stages. Interestingly, in the rostral bulb, NUCB2 mRNA was localized in the lining epithelium of young and old animals, while Nesf-1 immunoreactive cells were distributed in the submucosae. Taken together, our results represent a useful basis for gaining deeper knowledge regarding the mechanisms that regulate food intake during vertebrate aging.

Immunolocalization of Nesfatin-1 in the Gastrointestinal Tract of the Common Bottlenose Dolphin Tursiops truncatus

“…Very interestingly, Stengel and co-workers demonstrated that NUCB2/Nesf-1 expression levels in endocrine cells of gastric mucosa were 10-fold higher compared to brain levels, supporting the idea that the stomach is one of the main sites of production of circulating NUCB2/Nesf-1 [ 8 , 12 ]. Like in mammals, in teleost fish, Nesf-1 was expressed in both central and peripheral tissues, and different studies have demonstrated the highest NUCB2/Nesf-1 mRNA expression in the gastrointestinal tract [ 13 , 14 , 15 ], hypothesizing a common role of this peptide in vertebrates.…”

Age-Dependent Regulation of Notch Family Members in the Neuronal Stem Cell Niches of the Short-Lived Killifish Nothobranchius furzeri

“…In the last decade, our group has intensively studied the annual fish Nothobranchius furzeri as a new experimental model in biology. N. furzeri has gained recognition as an animal model for aging studies, and currently, it is extensively studied in an increasing number of laboratories worldwide (Kabiljo et al, 2019;Matsui et al, 2019;Montesano et al, 2019;Fumagalli et al, 2020;Hu et al, 2020;Kelmer et al, 2020;Wang et al, 2020). These fish inhabit ephemeral pools in the semiarid bushveld of Southern Mozambique characterized by scarce and erratic precipitations and have adapted to the seasonal drying of their environment by producing desiccation-resistant eggs that can remain dormant in the dry mud for 1 and maybe more years by entering into a diapause state (Genade et al, 2005;Cellerino et al, 2016;Kim et al, 2016).…”

Preclinical Models: Boosting Synergies for Improved Translation

“…Out of eleven papers, six are based on animal models [1][2][3][4][5][6], highlighting that these models still play a crucial role in translational medicine, even in a historical moment in which the need to find alternative methodologies is increasingly pressing.…”

“…More specifically, the paper analyses the potential of iPSC-endothelial cells in accelerating tissue regeneration and their suitability to enter progressively more clinical trials. The most represented research field in this Special Issue is tissue morphology [1][2][3]5] followed by tissue engineering [9][10][11] and neuroscience [1][2][3], with one article intercepting both these areas of expertise [12]. This latter work reports, indeed, a method to generate a three-dimensional neuronal system composed of cortical neurons and glial cells derived from iPSCs, suitable for drug screening and disease modeling.…”

“…It is worth noting how they both witness the increasing value of the short-lived African turquoise killifish Nothobranchius furzeri as an emerging vertebrate model in aging research. In particular, one paper describes, for the first time, the expression of neurotrophin-6 in different brain areas in both young and old animals [1], while the other one provides the first evidence of nucleobindin-2/nesfatin-1 expression and its role as a food intake regulator in vertebrate aging [3].…”