Current State of Modeling Human Psychiatric Disorders Using Zebrafish

Psychiatric disorders are highly prevalent brain pathologies that represent an urgent, unmet biomedical problem. Since reliable clinical diagnoses are essential for the treatment of psychiatric disorders, their animal models with robust, relevant behavioral and physiological endpoints become necessary. Zebrafish (Danio rerio) display well-defined, complex behaviors in major neurobehavioral domains which are evolutionarily conserved and strikingly parallel to those seen in rodents and humans. Although zebrafish are increasingly often used to model psychiatric disorders, there are also multiple challenges with such models as well. The field may therefore benefit from a balanced, disease-oriented discussion that considers the clinical prevalence, the pathological complexity, and societal importance of the disorders in question, and the extent of its detalization in zebrafish central nervous system (CNS) studies. Here, we critically discuss the use of zebrafish for modeling human psychiatric disorders in general, and highlight the topics for further in-depth consideration, in order to foster and (re)focus translational biological neuroscience research utilizing zebrafish. Recent developments in molecular biology research utilizing this model species have also been summarized here, collectively calling for a wider use of zebrafish in translational CNS disease modeling

Understanding CNS Effects of Antimicrobial Drugs Using Zebrafish Models

Antimicrobial drugs represent a diverse group of widely utilized antibiotic, antifungal, antiparasitic and antiviral agents. Their growing use and clinical importance necessitate our improved understanding of physiological effects of antimicrobial drugs, including their potential effects on the central nervous system (CNS), at molecular, cellular, and behavioral levels. In addition, antimicrobial drugs can alter the composition of gut microbiota, and hence affect the gut–microbiota–brain axis, further modulating brain and behavioral processes. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a powerful model system for screening various antimicrobial drugs, including probing their putative CNS effects. Here, we critically discuss recent evidence on the effects of antimicrobial drugs on brain and behavior in zebrafish, and outline future related lines of research using this aquatic model organism

Understanding CNS Effects of Antimicrobial Drugs Using Zebrafish Models

Antimicrobial drugs represent a diverse group of widely utilized antibiotic, antifungal, antiparasitic and antiviral agents. Their growing use and clinical importance necessitate our improved understanding of physiological effects of antimicrobial drugs, including their potential effects on the central nervous system (CNS), at molecular, cellular, and behavioral levels. In addition, antimicrobial drugs can alter the composition of gut microbiota, and hence affect the gut–microbiota–brain axis, further modulating brain and behavioral processes. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a powerful model system for screening various antimicrobial drugs, including probing their putative CNS effects. Here, we critically discuss recent evidence on the effects of antimicrobial drugs on brain and behavior in zebrafish, and outline future related lines of research using this aquatic model organism

Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish

The mammalian target of rapamycin (mTOR) is an important molecular regulator of cell growth and proliferation. Brain mTOR activity plays a crucial role in synaptic plasticity, cell development, migration and proliferation, as well as memory storage, protein synthesis, autophagy, ion channel expression and axonal regeneration. Aberrant mTOR signaling causes a diverse group of neurological disorders, termed ‘mTORopathies’. Typically arising from mutations within the mTOR signaling pathway, these disorders are characterized by cortical malformations and other neuromorphological abnormalities that usually co-occur with severe, often treatment-resistant, epilepsy. Here, we discuss recent advances and current challenges in developing experimental models of mTOR-dependent epilepsy and other related mTORopathies, including using zebrafish models for studying these disorders, as well as outline future directions of research in this field

Acute behavioral and Neurochemical Effects of Novel N-Benzyl-2-Phenylethylamine Derivatives in Adult Zebrafish

Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH3, -OCF3, -F, -Cl, and -Br substitutions in the ortho position of the phenyl ring of the N-benzyl moiety, assessing their acute behavioral and neurochemical effects in the adult zebrafish. Overall, substitutions in the Overall, substitutions in the N-benzyl moiety modulate locomotion, and substitutions in the phenethylamine moiety alter zebrafish anxiety-like behavior, also affecting the brain serotonin and/or dopamine turnover. The 24H-NBOMe(F) and 34H-NBOMe(F) treatment also reduced zebrafish despair-like behavior. Computational analyses of zebrafish behavioral data by artificial intelligence identified several distinct clusters for these agents, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe, and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl, and 34H-NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl, and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) drugs. Our computational analyses also revealed phenotypic similarity of the behavioral activity of some NBPEAs to that of selected conventional serotonergic and antiglutamatergic hallucinogens. In silico functional molecular activity modeling further supported the overlap of the drug targets for NBPEAs tested here and the conventional serotonergic and antiglutamatergic hallucinogens. Overall, these findings suggest potent neuroactive properties of several novel synthetic NBPEAs, detected in a sensitive in vivo vertebrate model system, the zebrafish, raising the possibility of their potential clinical use and abuse