Identification and Expression of Neurotrophin-6 in the Brain of Nothobranchius furzeri: One More Piece in Neurotrophin Research

Abstract

Neurotrophins contribute to the complexity of vertebrate nervous system, being involved in cognition and memory. Abnormalities associated with neurotrophin synthesis may lead to neuropathies, neurodegenerative disorders and age-associated cognitive decline. The genome of teleost fishes contains homologs of some mammalian neurotrophins as well as a gene coding for an additional neurotrophin (NT-6). In this study, we characterized this specific neurotrophin in the short-lived fish Nothobranchius furzeri, a relatively new model for aging studies. Thus, we report herein for the first time the age-related expression of a neurotrophin in a non-mammalian vertebrate. Interestingly, we found comparable expression levels of NT-6 in the brain of both young and old animals. More in detail, we used a locked nucleic acid probe and a riboprobe to investigate the neuroanatomical distribution of NT-6 mRNA revealing a significant expression of the neurotrophin in neurons of the forebrain (olfactory bulbs, dorsal and ventral telencephalon, and several diencephalic nuclei), midbrain (optic tectum, longitudinal tori, and semicircular tori), and hindbrain (valvula and body of cerebellum, reticular formation and octavolateral area of medulla oblongata). By combining in situ hybridization and immunohistochemistry, we showed that NT-6 mRNA is synthesized in mature neurons. These results contribute to better understanding the evolutionary history of neurotrophins in vertebrates, and their role in the adult brain.

Cholinergic System and NGF Receptors: Insights from the Brain of the Short-Lived Fish Nothobranchius furzeri

“…In the brain of old animals, we observed a decreased number of p75/NGFR expressing cells and an unaltered number of positive NTRK1/NTRKA expressing cells during aging. This pattern denotes a region-specific expression of the two nerve growth factors receptors encoding genes, when compared to the neuroanatomical distribution of the neurotrophin family ligands analyzed in the adult brain of N. furzeri [ 10 , 11 , 12 , 13 ] Indeed NGF, BDNF, NT-4 and NT-6 are expressed in all regions of the adult brain, although with different patterns of expression. This raises the need of further investigations to explore the physiological role of neurotrophins and their receptors in the fish brain.…”

“…Tissues were taken out of RNAlater and cleaned with sterile pipettes. N. furzeri total RNA was isolated from 12 animals with QIAzol (Qiagen), as previously described [ 10 ]. Homogenization was performed using a TissueLyzer II (Qiagen) at 20 Hz for 2–3 × 1 min.…”

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].…”