Numerous neurodegenerative and psychiatric disorders are associated with deficits in executive functions such as working memory and cognitive flexibility. Progress in developing effective treatments for disorders may benefit from targeting these cognitive impairments, the success of which is predicated on the development of animal models with validated behavioural assays. Zebrafish offer a promising model for studying complex brain disorders, but tasks assessing executive function are lacking. The Free-movement pattern (FMP) Y-maze combines aspects of the common Y-maze assay, which exploits the inherent motivation of an organism to explore an unknown environment, with analysis based on a series of sequential two-choice discriminations. We validate the task as a measure of working memory and executive function by comparing task performance parameters in adult zebrafish treated with a range of glutamatergic, cholinergic and dopaminergic drugs known to impair working memory and cognitive flexibility. We demonstrate the cross-species validity of the task by assessing performance parameters in adapted versions of the task for mice and Drosophila, and finally a virtual version in humans, and identify remarkable commonalities between vertebrate species' navigation of the maze. Together, our results demonstrate that the FMP Y-maze is a sensitive assay for assessing working memory and cognitive flexibility across species from invertebrates to humans, providing a simple and widely applicable behavioural assay with exceptional translational relevance.

No abstract

No abstract

Paraquat (PQ) administration consists in a chemical model that mimics phenotypes observed in Parkinson's disease (PD), due to its ability to induce changes in dopaminergic system and oxidative stress. The aim of this study was to evaluate the actions of PQ in behavioral functions of adult zebrafish and its influence on oxidative stress biomarkers in brain samples. PQ (20 mg/kg) was administered intraperitoneally with six injections for 16 days (one injection every 3 days). PQ-treated group showed a significant decrease in the time spent in the bottom section and a shorter latency to enter the top area in the novel tank test. Moreover, PQ-exposed fish showed a significant decrease in the number and duration of risk assessment episodes in the light-dark test, as well as an increase in the agonistic behavior in the mirror-induced aggression (MIA) test. PQ induced brain damage by decreasing mitochondrial viability. Concerning the antioxidant defense system, PQ increased catalase (CAT) and glutathione peroxidase (GPx) activities, as well as the non-protein sulfhydryl content (NPSH), but did not change ROS formation and decreased lipid peroxidation. We demonstrate, for the first time, that PQ induces an increase in aggressive behavior, alters non-motor patterns associated to defensive behaviors, and changes redox parameters in zebrafish brain. Overall, our findings may serve as useful tools to investigate the interaction between behavioral and neurochemical impairments triggered by PQ administration in zebrafish.

Neurodevelopmental disorders (NDDs) caused by aberrant brain growth and development are lifelong , debilitating illnesses that markedly impair the quality of life. Animal models are a valuable tool for studying NDD pathobiology and therapies. Mounting evidence suggests the zebrafish (Danio rerio) as a useful model organism to study NDDs with high physiological homology to humans and sensitivity to pharmacological and genetic manipulations. Here, we summarize experimental models of NDDs in zebrafish and highlight the growing translational significance of zebrafish NDD-related phenotypes. We also emphasize the need in further development of zebrafish models of NDDs to improve our understanding of their pathogenesis and therapeutic treatments.

No abstract

PurposeThis study aimed to determine whether l-arginine supplementation lasting for 18 months maintained long-lasting effects on diabetes incidence, insulin secretion and sensitivity, oxidative stress, and endothelial function during 108 months among subjects at high risk of developing type 2 diabetes.MethodsOne hundred and forty-four middle-aged subjects with impaired glucose tolerance and metabolic syndrome were randomized in 2006 to an l-arginine supplementation (6.4 g orally/day) or placebo therapy lasting 18 months. This period was followed by a 90-month follow-up. The primary outcome was a diagnosis of diabetes during the 108 month study period. Secondary outcomes included changes in insulin secretion (proinsulin/c-peptide ratio), insulin sensitivity (IGI/HOMA-IR), oxidative stress (AOPPs), and vascular function. After the 18 month participation, subjects that were still free of diabetes and willing to continue their participation (104 subjects) were further followed until diabetes diagnosis, with a time span of about 9 years from baseline.ResultsAlthough results derived from the 18 month of the intervention study demonstrated no differences in the probability of becoming diabetics, at the end of the study, the cumulative incidence of diabetes was of 40.6% in the l-arginine group and of 57.4% in the placebo group. The adjusted HR for diabetes (l-arginine vs. placebo) was 0.66; 95% CI 0.48, 0.91; p < 0.02). Proinsulin/c-peptide ratio (p < 0.001), IGI/HOMA-IR (p < 0.01), and AOPP (p < 0.05) levels were ameliorated in l-arginine compared to placebo.ConclusionsThese results may suggest that the administration of l-arginine could delay the development of T2DM for a long period. This effect could be mediated, in some extent, by l-arginine-induced reduction in oxidative stress.

Once considered a uniquely human attribute, behavioral laterality has proven to be ubiquitous among non-human animals, and is associated with several neurophenotypes in rodents and fishes. Zebrafish (Danio rerio) is a versatile vertebrate model system widely used in translational neuropsychiatric research owing to their highly conserved genetic homology, well-characterized physiological responses, and extensive behavioral repertoire. Although spontaneous left- and right-biased responses, and associated behavioral domains (e.g., stress reactivity, aggression, and learning), have previously been observed in other teleost species, no information relating to whether spontaneous motor left–right-bias responses of zebrafish predicts other behavioral domains has been described. Thus, we aimed to investigate the existence and incidence of natural left–right bias in adult zebrafish, exploiting an unconditioned continuous free movement pattern (FMP) Y-maze task, and to explore the relationship of biasedness on performance within different behavioral domains. This included learning about threat cues in a Pavlovian fear conditioning test, and locomotion and anxiety-related behavior in the novel tank diving test. Although laterality did not change locomotion or anxiety-related behaviors, we found that biased animals displayed a different search strategy in the Y-maze, making them easily discernable from their unbiased counterparts, and increased learning associated to fear cues. In conclusion, we showed, for the first time, that zebrafish exhibit a natural manifestation of motor behavioral lateralization which can influence aversive learning responses.