Neurodegeneration is a major cause of Alzheimer’s, Parkinson’s, Huntington’s, multiple and amyotrophic lateral sclerosis, pontocerebellar hypoplasia, dementia and other related brain disorders. Their ...complex pathogenesis commonly includes genetic and neurochemical deficits, misfolded protein toxicity, demyelination, apoptosis and mitochondrial dysfunctions. Albeit differing in specific underlying mechanisms, neurodegenerative disorders typically display evolutionarily conserved mechanisms across taxa. Here, we review the role of zebrafish models in recapitulating major human and rodent neurodegenerative conditions, demonstrating this species as a highly relevant experimental model for research on neurodegenerative diseases, and discussing how these fish models can further clarify the underlying genetic, neurochemical, neuroanatomical and behavioral pathogenic mechanisms.
•Zebrafish is a highly relevant model species in neurodegenerative research.•Zebrafish models can help clarify key pathogenic mechanisms of neurodegeneration.•Neurodegenerative disorders have evolutionarily conserved mechanisms across taxa.•Neurodegeneration involves complex genetic and molecular deficits across taxa.
Towards Zebrafish Models of CNS Channelopathies Kolesnikova, Tatiana O; Demin, Konstantin A; Costa, Fabiano V ...
International journal of molecular sciences,
11/2022, Letnik:
23, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Channelopathies are a large group of systemic disorders whose pathogenesis is associated with dysfunctional ion channels. Aberrant transmembrane transport of K
, Na
, Ca
and Cl
by these channels in ...the brain induces central nervous system (CNS) channelopathies, most commonly including epilepsy, but also migraine, as well as various movement and psychiatric disorders. Animal models are a useful tool for studying pathogenesis of a wide range of brain disorders, including channelopathies. Complementing multiple well-established rodent models, the zebrafish (
) has become a popular translational model organism for neurobiology, psychopharmacology and toxicology research, and for probing mechanisms underlying CNS pathogenesis. Here, we discuss current prospects and challenges of developing genetic, pharmacological and other experimental models of major CNS channelopathies based on zebrafish.
Widespread, debilitating and often treatment-resistant, depression and other stress-related neuropsychiatric disorders represent an urgent unmet biomedical and societal problem. Although animal ...models of these disorders are commonly used to study stress pathogenesis, they are often difficult to translate across species into valuable and meaningful clinically relevant data. To address this problem, here we utilized several cross-species/cross-taxon approaches to identify potential evolutionarily conserved differentially expressed genes and their sets. We also assessed enrichment of these genes for transcription factors DNA-binding sites down- and up- stream from their genetic sequences. For this, we compared our own RNA-seq brain transcriptomic data obtained from chronically stressed rats and zebrafish with publicly available human transcriptomic data for patients with major depression and their respective healthy control groups. Utilizing these data from the three species, we next analyzed their differential gene expression, gene set enrichment and protein-protein interaction networks, combined with validated tools for data pooling. This approach allowed us to identify several key brain proteins (GRIA1, DLG1, CDH1, THRB, PLCG2, NGEF, IKZF1 and FEZF2) as promising, evolutionarily conserved and shared affective 'hub' protein targets, as well as to propose a novel gene set that may be used to further study affective pathogenesis. Overall, these approaches may advance cross-species brain transcriptomic analyses, and call for further cross-species studies into putative shared molecular mechanisms of affective pathogenesis.
Cerebral cortex is found only in mammals and is particularly prominent and developed in humans. Various rodent models with fully or partially ablated cortex are commonly used to probe the role of ...cortex in brain functions and its multiple subcortical projections, including pallium, thalamus and the limbic system. Various rodent models are traditionally used to study the role of cortex in brain functions. A small teleost fish, the zebrafish (Danio rerio), has gained popularity in neuroscience research, and albeit (like other fishes) lacking cortex, its brain performs well some key functions (e.g., memory, consciousness and motivation) with complex, context-specific and well-defined behaviors. Can rodent and zebrafish models help generate insights into the role of cortex in brain functions, and dissect its cortex-specific (vs. non-cortical) functions? To address this conceptual question, here we evaluate brain functionality in intact vs. decorticated rodents and further compare it in the zebrafish, a naturally occurring acortical species. Overall, comparing cortical and acortical rodent models with naturally acortical zebrafish reveals both distinct and overlapping contributions of neocortex and ‘precortical’ zebrafish telencephalic regions to higher brain functions. Albeit morphologically different, mammalian neocortex and fish pallium may possess more functional similarities than it is presently recognized, calling for further integrative research utilizing both cortical and decorticated/acortical vertebrate model organisms.
•Animal models are traditionally used to study the role of cortex in brain functions.•Decorticated rodents and naturally acortical vertebrates help probe the role of cortex.•The zebrafish is a useful model organism in neuroscience research.•Albeit lacking cortex, zebrafish help generate insights into the role of cortex in brain functions.
Delirium is an acute neuropsychiatric syndrome characterized by impaired behavior and cognition. Although the syndrome has been known for millennia, its CNS mechanisms and risk factors remain poorly ...understood. Experimental animal models, especially rodent-based, are commonly used to probe various pathogenetic aspects of delirium. Complementing rodents, the zebrafish (Danio rerio) emerges as a promising novel model organism to study delirium. Zebrafish demonstrate high genetic and physiological homology to mammals, easy maintenance, robust behaviors in various sensitive behavioral tests, and the potential to screen for pharmacological agents relevant to delirium. Here, we critically discuss recent developments in the field, and emphasize the developing utility of zebrafish models for translational studies of delirium and deliriant drugs. Overall, the zebrafish represents a valuable and promising aquatic model species whose use may help understand delirium etiology, as well as develop novel therapies for this severely debilitating disorder.
Human neocortex controls and integrates cognition, emotions, perception and complex behaviors. Aberrant cortical development can be triggered by multiple genetic and environmental factors, causing ...cortical malformations. Animal models, especially rodents, are a valuable tool to probe molecular and physiological mechanisms of cortical malformations. Complementing rodent studies, the zebrafish (Danio rerio) is an important model organism in biomedicine. Although the zebrafish (like other fishes) lacks neocortex, here we argue that this species can still be used to model various aspects and brain phenomena related to human cortical malformations. We also discuss novel perspectives in this field, covering both advantages and limitations of using mammalian and zebrafish models in cortical malformation research. Summarizing mounting evidence, we also highlight the importance of translationally-relevant insights into the pathogenesis of cortical malformations from animal models, and discuss future strategies of research in the field.
•Cortical malformations are a diverse family of rare human brain disorders.•Mammalian models are widely used to probe pathobiology of cortical malformations.•Lacking neocortex, zebrafish are widely used to study brain disorders.•Mounting evidence suggests zebrafish as a novel model for cortical malformations research.•We discuss advantages and limitations of animal models of cortical malformations.
Abnormal repetitive behaviors (ARBs) are a prominent symptom of numerous human brain disorders and are commonly seen in rodent models as well. While rodent studies of ARBs continue to dominate the ...field, mounting evidence suggests that zebrafish (Danio rerio) also display ARB-like phenotypes and may therefore be a novel model organism for ARB research. In addition to clear practical research advantages as a model species, zebrafish share high genetic and physiological homology to humans and rodents, including multiple ARB-related genes and robust behaviors relevant to ARB. Here, we discuss a wide spectrum of stereotypic repetitive behaviors in zebrafish, data on their genetic and pharmacological modulation, and the overall translational relevance of fish ARBs to modeling human brain disorders. Overall, the zebrafish is rapidly emerging as a new promising model to study ARBs and their underlying mechanisms.
Anxiety is the most prevalent brain disorder and a common cause of human disability. Animal models are critical for understanding anxiety pathogenesis and its pharmacotherapy. The zebrafish (Danio ...rerio) is increasingly utilized as a powerful model organism in anxiety research and anxiolytic drug screening. High similarity between human, rodent and zebrafish molecular targets implies shared signaling pathways involved in anxiety pathogenesis. However, mounting evidence shows that zebrafish behavior can be modulated by drugs beyond conventional anxiolytics or anxiogenics. Furthermore, these effects may differ from human and/or rodent responses, as such ‘unconventional’ drugs may affect zebrafish behavior despite having no such profiles (or exerting opposite effects) in humans or rodents. Here, we discuss the effects of several putative unconventional anxiotropic drugs (aspirin, lysergic acid diethylamide (LSD), nicotine, naloxone and naltrexone) and their potential mechanisms of action in zebrafish. Emphasizing the growing utility of zebrafish models in CNS drug discovery, such unconventional anxiety pharmacology may provide important, evolutionarily relevant insights into complex regulation of anxiety in biological systems. Albeit seemingly complicating direct translation from zebrafish into clinical phenotypes, this knowledge may instead foster the development of novel CNS drugs, eventually facilitating innovative treatment of patients based on novel ‘unconventional’ targets identified in fish models.
•Animal models are critical tool for understanding anxiety pathogenesis.•The zebrafish is a powerful model organism in anxiety research.•Zebrafish behavior can be modulated by various anxiotropic drugs.•Discussed here, some effects in zebrafish differ from conventional anxiotropic drugs.
Zebrafish (Danio rerio) are rapidly emerging in biomedicine as promising tools for disease modelling and drug discovery. The use of zebrafish for neuroscience research is also growing rapidly, ...necessitating novel reliable and unbiased methods of neurophenotypic data collection and analyses. Here, we applied the artificial intelligence (AI) neural network-based algorithms to a large dataset of adult zebrafish locomotor tracks collected previously in a series of in vivo experiments with multiple established psychotropic drugs. We first trained AI to recognize various drugs from a wide range of psychotropic agents tested, and then confirmed prediction accuracy of trained AI by comparing several agents with known similar behavioral and pharmacological profiles. Presenting a framework for innovative neurophenotyping, this proof-of-concept study aims to improve AI-driven movement pattern classification in zebrafish, thereby fostering drug discovery and development utilizing this key model organism.
•Zebrafish is a promising tool for disease modelling and drug discovery.•Here, we applied the artificial intelligence (AI) algorithms to zebrafish locomotor tracks.•We trained AI to recognize various drugs from a wide range of psychotropic agents.•We also reconfirmed prediction accuracy by comparing agents with known profiles.•This proof-of-concept study shows AI-driven movement pattern classification in zebrafish.
Anticholinergic drugs based on tropane alkaloids, including atropine, scopolamine, and hyoscyamine, have been used for various medicinal and toxic purposes for millennia. These drugs are competitive ...antagonists of acetylcholine muscarinic (M-) receptors that potently modulate the central nervous system (CNS). Currently used clinically to treat vomiting, nausea, and bradycardia, as well as alongside other anesthetics to avoid vagal inhibition, these drugs also evoke potent psychotropic effects, including characteristic delirium-like states with hallucinations, altered mood, and cognitive deficits. Given the growing clinical importance of anti-M deliriant hallucinogens, here we discuss their use and abuse, clinical importance, and the growing value in preclinical (experimental) animal models relevant to modeling CNS functions and dysfunctions.
PDF
