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A growing body of evidence suggests that the biological effects of polyphenols are not restricted to antioxidant activity, but they exert a wide range of modulatory effects on metabolic pathways, cellular signaling and gene expression. In this study, we tested the minimum safe concentration of gallic acid (GA) in 72 hpf zebrafish larvae in order to evaluate the effects on the central nervous system and the behavioral response. We showed that a short exposure (30 min) induces the depletion of the two main excitatory and inhibitory neurotransmitters, Glu and GABA, respectively, in the larval nervous system. The acute impairment of GABAergic-glutamatergic balance was paralleled by an increase of the fosab neuronal activity marker in specific brain areas, such as the forebrain, olfactory bulbs, pallial area, ventral midbrain, tegmentum, and the medulla oblongata ventral area. The neuronal excitation was mirrored by the increased cumulative motor response. The inhibition of the olfactory epithelium with brief cadmium exposition suggests a direct involvement of olfaction in the larvae response to GA. Our results demonstrate that a brief exposure to GA induces motoneuronal hyperexcitability in zebrafish. The behavioral response was probably elicited through the activation of an odorous, or chemical, stimulus. The specificity of the activated neuronal territories suggests the involvement of additional signaling pathways. Although the underlying molecular mechanisms remain to be elucidated, our data support the hypothesis that GA acts as an excitatory molecule, capable of inducing a specific nerve response. These results offer a new vision on potential effects of GA., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The complexes formed by BCL10, MALT1 and specific members of the family of CARMA proteins (CBM complex), have recently focused much attention because they represent a central hub regulating activation of the transcription factor NF-κB following various cellular stimulations. In this manuscript, we report the functional characterization of a Danio rerio 241 amino acids polypeptide ortholog of the Caspase recruiting domain (CARD)-containing protein BCL10. Biochemical studies show that zebrafish Bcl10 (zBcl10) dimerizes and binds to components of the CBM complex. Fluorescence microscopy observations demonstrate that zBcl10 forms cytoplasmic filaments similar to that formed by human BCL10 (hBCL10). Functionally, in human cells zBcl10 is more effective in activating NF-κB compared to hBCL10, possibly due to the lack of carboxy-terminal inhibitory serine residues present in the human protein. Also, depletion experiments carried out through expression of short hairpin RNAs targeting hBCL10 indicate that zBcl10 can functionally replace the human protein. Finally, we show that the zebrafish cell line PAC2 is suitable to carry out reporter assays for monitoring the activation state of NF- kB transcription factor. In conclusion, this work shows that zebrafish may excellently serve as a model organism to study complex and intricate signal transduction pathways, such as those that control NF-κB activation.

Simple Summary: With the increase in global population the production of animal proteins becomes increasingly crucial. Aquaculture is the first animal protein supply industry for human consumption. Intensive farming techniques are employed to increase productivity, but these may cause stressful conditions for fish, resulting in impaired growth and poor health conditions. Intestinal inflammation is one of the most common diseases of fish in intensive farming. Intestinal inflammation is usually accompanied by an alteration of the microbiota or dysbiosis. Inflammation and dysbiosis are so tightly intertwined that inflammation may contribute to or result from dysregulation of gut microbiota. Natural substances of plant origin rich in bioactive molecules or more simply phytochemicals, have been proved to be able to reduce inflammation and improve the general health status in various commercially relevant species. In this study, we evaluated the effect of tannins, a class of polyphenols, the most abundant phytochemicals, on intestinal inflammation and microbiota in zebrafish (Danio rerio), a small freshwater fish become an attractive biomedicine and aquaculture animal model during the last decades. The zebrafish has been employed in a vast array of studies aiming at investigating the essential processes underlying intestinal inflammation and injury due to its conservative gut morphology and functions. In this study, we administered a diet enriched with chestnut shell extract rich in tannins to a zebrafish model of intestinal inflammation. The treatment ameliorated the damaged intestinal morphophysiology and the microbiota asset. Our results sustain that products of natural origin with low environmental impact and low cost, such as tannins, may help to ease some of the critical issues affecting the aquaculture sector. The aim of the present study was to test the possible ameliorative efficacy of phytochemicals such as tannins on intestinal inflammation and dysbiosis. The effect of a chestnut shell (Castanea sativa) extract (CSE) rich in polyphenols, mainly represented by tannins, on k-carrageenan-induced intestinal inflammation in adult zebrafish (Danio rerio) was tested in a feeding trial. Intestinal inflammation was induced by 0.1% k-carrageenan added to the diet for 10 days. CSE was administered for 10 days after k-carrageenan induced inflammation. The intestinal morphology and histopathology, cytokine expression, and microbiota were analyzed. The k-carrageenan treatment led to gut lumen expansion, reduction of intestinal folds, and increase of the goblet cells number, accompanied by the upregulation of pro-inflammatory factors (TNFα, COX2) and alteration in the number and ratio of taxonomic groups of bacteria. CSE counteracted the inflammatory status enhancing the growth of health helpful bacteria (Enterobacteriaceae and Pseudomonas), decreasing the pro-inflammatory factors, and activating the anti-inflammatory cytokine IL-10. In conclusion, CSE acted as a prebiotic on zebrafish gut microbiota, sustaining the use of tannins as food additives to ameliorate the intestinal inflammation. Our results may be relevant for both aquaculture and medical clinic fields. [ABSTRACT FROM AUTHOR]

Simple Summary: The obesity induced by overconsumption of nutrients leads to systemic inflammation and alters metabolic homeostasis by acting on central nervous system and peripheral tissues such as intestine. The 3,5-diiodo-L-thyronine (3,5-T2) is well-known for its positive role on fat mass and lipid metabolism, and at date, it is widely used as a drug for the treatment of obesity. However, the safe and effective dose as well as the possible adverse effects of this molecule have not been sufficiently explored. In this study, we analyzed the role of 3,5-T2 in regulating central and peripheral inflammation in diet-induced obese (D.I.O.) model of zebrafish. We found that 3,5-T2 sustained the intestinal alteration caused by D.I.O., as indicated by the high levels of pro-inflammatory cytokines, accompanied by a significant effect of 3,5-T2 on body weight and central inflammation in D.I.O. zebrafish. Therefore, the suggested potential use of 3,5-T2 to contrast obesity should be viewed with caution. We conclude that the zebrafish model can help to better understand the fundamental beneficial and side effects of 3,5-T2, which is of great importance to define the possible use of this metabolite of thyroid hormones as a drug in different diseases including obesity. The 3,5-diiodo-L-thyronine (3,5-T2) is an endogenous metabolite of thyroid hormones, whose administration to rodents fed high-fat diet (HFD) prevents body weight increase and reverts the expression pattern of pro-inflammatory factors associated to HFD. The diet-induced obese (D.I.O.) zebrafish (Danio rerio) has been recently used as an experimental model to investigate fundamental processes underlying central and peripheral obesity-driven inflammation. Herein, we aim to understand the role of 3,5-T2 in regulating central and peripheral inflammation in D.I.O. model of zebrafish. 3,5-T2 (10 nM and 100 nM) was administered with the obesity-inducing diet (D.I.O. with 3,5-T2) or after 4 weeks of obesity-inducing diet (D.I.O. flw 3,5-T2). 3,5-T2 significantly increased the body weight and serum triglyceride levels in D.I.O. zebrafish in both conditions. Moreover, 3,5-T2 sustained or increased inflammation in the anterior (AI) and mid (MI) intestine when administered with the obesity-inducing diet, as indicated by the immunoexpression of the inflammatory markers tumor-necrosis factor-α (TNFα), cyclooxygenase 2 (COX2), calnexin, caspase 3, and proliferating cell nuclear antigen (PCNA). On the contrary, when 3,5-T2 was administered after the obesity-inducing diet, partly reverted the intestinal alteration induced by D.I.O. In addition, brain inflammation, as indicated by the increase in the activation of microglia, was detected in D.I.O. zebrafish and D.I.O. treated with 3,5-T2. These findings reveal that the effects of 3,5-T2 on fish intestine and brain can deviate from those shown in obese mammals, opening new avenues to the investigation of the potential impact of this thyroid metabolite in different diseases including obesity. [ABSTRACT FROM AUTHOR]