Neurotrophins and Trk Neurotrophin Receptors in the Retina of Adult Killifish (Nothobranchius guentheri).

Specific subpopulations of neurons in nerve and sensory systems must be developed and maintained, and this is accomplished in significant part by neurotrophins (NTs) and the signaling receptors on which they act, called tyrosine protein kinase receptors (Trks). The neurotrophins-tyrosine protein kinase receptors (NTs/Trks) system is involved in sensory organ regulation, including the visual system. An NTs/Trks system alteration is associated with neurodegeneration related to aging and diseases, including retinal pathologies. An emergent model in the field of translational medicine, for instance, in aging study, is the annual killifish belonging to the Nothobranchius genus, thanks to its short lifespan. Members of this genus, such as Nothobranchius guentheri, and humans share a similar retinal stratigraphy. Nevertheless, according to the authors' knowledge, the occurrence and distribution of the NTs/Trks system in the retina of N. guentheri has never been investigated before. Therefore, the present study aimed to localize neurotrophin BDNF, NGF, and NT-3 and TrkA, TrkB, and TrkC receptors in the N. guentheri retina using the immunofluorescence method. The present investigation demonstrates, for the first time, the occurrence of the NTs/Trks system in N. guentheri retina and, consequently, the potential key role of these proteins in the biology and survival of the retinal cells.

Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders.

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders.

Antioxidant and Hepatoprotective Effect of a Nutritional Supplement with Silymarin Phytosome, Choline Chloride, l-Cystine, Artichoke, and Vitamin E in Dogs.

Phytotherapy has been promoted for the treatment of liver diseases in dogs. The interest in identifying the antioxidant/hepatoprotective potential of various plants is increasing. Every 10 days for 30 days, forty dogs were subjected to blood sampling and hepatic ultrasound assessment. Clinically healthy dogs (group A) and dogs with liver enzyme and ultrasound hepatic aspects and sizes outside the physiological range (group B) were divided into two subgroups. Every day for 30 days, one subgroup received Epacare pet + pasta® and the other received a placebo. Differences due to groups were observed in dROM, SHp, AST and LDH serum concentrations. The administration of Epacarepet + pasta® for 30 days had an influence on the serum concentration of dROMs, SHp, AST, ALT, ALP, LDH, and urea. The application of paired Student's t-test showed a decrease in the longitudinal and transverse liver axis size. In conclusion, feed supplementation with Epacare pet + pasta® had a beneficial effect on the antioxidant status and liver enzymes in animals with liver enzymatic alterations and in healthy dogs.

Localization of Neurotrophin Specific Trk Receptors in Mechanosensory Systems of Killifish (Nothobranchius guentheri).

Neurotrophins (NTs) and their signal-transducing Trk receptors play a crucial role in the development and maintenance of specific neuronal subpopulations in nervous and sensory systems. NTs are supposed to regulate two sensory systems in fish, the inner ear and the lateral line system (LLS). The latter is one of the major mechanosensory systems in fish. Considering that annual fishes of the genus Nothobranchius, with their short life expectancy, have become a suitable model for aging studies and that the occurrence and distribution of neurotrophin Trk receptors have never been investigated in the inner ear and LLS of killifish (Nothobranchius guentheri), our study aimed to investigate the localization of neurotrophin-specific Trk receptors in mechanosensory systems of N. guentheri. For histological and immunohistochemical analysis, adult specimens of N. guentheri were processed using antibodies against Trk receptors and S100 protein. An intense immunoreaction for TrkA and TrkC was found in the sensory cells of the inner ear as well as in the hair cells of LLS. Moreover, also the neurons localized in the acoustic ganglia displayed a specific immunoreaction for all Trk receptors (TrkA, B, and C) analyzed. Taken together, our results demonstrate, for the first time, that neurotrophins and their specific receptors could play a pivotal role in the biology of the sensory cells of the inner ear and LLS of N. guentheri and might also be involved in the hair cells regeneration process in normal and aged conditions.

Zebrafish and Flavonoids: Adjuvants against Obesity.

Obesity is a pathological condition, defined as an excessive accumulation of fat, primarily caused by an energy imbalance. The storage of excess energy in the form of triglycerides within the adipocyte leads to lipotoxicity and promotes the phenotypic switch in the M1/M2 macrophage. These changes induce the development of a chronic state of low-grade inflammation, subsequently generating obesity-related complications, commonly known as metabolic syndromes. Over the past decade, obesity has been studied in many animal models. However, due to its competitive aspects and unique characteristics, the use of zebrafish has begun to gain traction in experimental obesity research. To counteract obesity and its related comorbidities, several natural substances have been studied. One of those natural substances reported to have substantial biological effects on obesity are flavonoids. This review summarizes the results of studies that examined the effects of flavonoids on obesity and related diseases and the emergence of zebrafish as a model of diet-induced obesity.

Zebrafish as a Useful Model to Study Oxidative Stress-Linked Disorders: Focus on Flavonoids.

The zebrafish is considered one of the most versatile experimental animal models. The transparency of the embryos, the small size, the rapid development and the homology with higher vertebrates have made the zebrafish a valuable model also for drug screening. Its use is closely related for the determination of bioactivity, toxicity and off-target side effects of novel drug candidates, which also allows a thorough evaluation of new targets; thus, it may represent a suitable model for drug screening and the optimization of novel candidates. Flavonoids are polyphenolic compounds widely present in fruits, vegetables and cereals. Polyphenols are important for both plants and humans, considering their involvement in defense mechanisms, particularly against oxidative stress. They protect plants from biotic and abiotic stressors and prevent or treat oxidative-based human diseases. For these reasons, polyphenols are used as nutraceuticals, functional foods and supplements by the pharmaceutical industry. Therefore, the most relevant findings on zebrafish as a useful experimental model to study oxidative stress-linked disorders, focusing on the biological activities of flavonoids, are here summarized and reviewed.

The Effect of Orally Supplemented Melatonin on Larval Performance and Skeletal Deformities in Farmed Gilthead Seabream (Sparus aurata).

The gilthead seabream larval rearing in continuous light is common in most Mediterranean hatcheries to stimulate larval length growth and increase food consumption. Several studies have shown that continuous light affects larval development and increases the prevalence of skeletal deformities. Melatonin is a crucial pineal neurohormone that displays daily secretion patterns, stimulates cell proliferation and embryonic development in Atlantic salmon and zebrafish, and improves osseointegration in mice and humans. However, no studies have examined the effects of orally supplemented melatonin on skeletal deformities in Sparus aurata larvae. We administered exogenous melatonin to gilthead seabream larvae via enriched rotifers and nauplii of Artemia. Exogenous melatonin induced bone deformities and stimulated parathyroid hormone-related protein-coding gene (PTHrP) mRNA expression. In addition to the melatonin-induced PTHrP high expression level, the recorded non coordinated function of skeletal muscle and bone during growth can be the fountainhead of bone deformities. Both myosin light chain 2 (mlc2) and bone gamma-carboxyglutamate protein-coding gene (bglap) expression levels were significantly affected by melatonin administration in an inverse dose-response manner during the exogenous melatonin administration. This is the first study to report the effect of inducing melatonin bone deformities on Sparus aurata larvae reared under ordinary hatchery conditions.

Topographical and drug specific sensitivity of hair cells of the zebrafish larvae to aminoglycoside-induced toxicity.

The hair cells of the lateral line system of fishes are morphologically and physiologically similar to the hair cells of the mammalian inner ear, also sharing its molecular characteristics. For this reason, it has been used as a powerful animal model to analyze in vivo ototoxicity. In this work, we examined the dose-dependent effects of two potent ototoxic aminoglycosides, neomycin and gentamicin, on the hair cells of two selected neuromasts (L1 and T1, the first of the trunk and the terminal located in the fin, respectively) of the lateral line in the ET4 transgenic zebrafish line. The hair cells of this strain selectively and constitutively display fluorescence. The fish were treated for 24 h at different doses (1, 2.5, 5, 10 and 100 µM levels) of both aminoglycosides. Immediately after treatment the morphology and the number of cells in L1 and T were analyzed under a fluorescence microscope. The results show that neomycin and gentamicin have different effects on the hair cell death at the same concentration, showing also different toxicity in L1 and T1 neuromasts. The toxicity observed in the hair cells of T1 neuromast was less than in L1 especially for the gentamicin treatment. These results demonstrate different sensitivity of hair cells of the lateral line to ototoxic drugs according to topographical localization and suggest the in vivo assay of the L1 neuromast of zebrafish larva and low doses of neomycin as an ideal model to study ototoxicity induced by aminoglycosides.