Darya A. Meshalkina

Bio: Darya A. Meshalkina is an academic researcher from Saint Petersburg State University. The author has contributed to research in topics: Zebrafish & Slow-wave sleep. The author has an hindex of 15, co-authored 28 publications receiving 663 citations. Previous affiliations of Darya A. Meshalkina include Russian Academy of Sciences.

Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests.

Abstract: Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs.

Zebrafish Models in NeuroPsychopharmacology and CNS Drug Discovery

Abstract: Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets.

Modeling consequences of prolonged strong unpredictable stress in zebrafish: Complex effects on behavior and physiology

Abstract: Chronic stress is the major pathogenetic factor of human anxiety and depression. Zebrafish (Danio rerio) have become a novel popular model species for neuroscience research and CNS drug discovery. The utility of zebrafish for mimicking human affective disorders is also rapidly growing. Here, we present a new zebrafish model of clinically relevant, prolonged unpredictable strong chronic stress (PUCS). The 5-week PUCS induced overt anxiety-like and motor retardation-like behaviors in adult zebrafish, also elevating whole-body cortisol and proinflammatory cytokines - interleukins IL-1β and IL-6. PUCS also elevated whole-body levels of the anti-inflammatory cytokine IL-10 and increased the density of dendritic spines in zebrafish telencephalic neurons. Chronic treatment of fish with an antidepressant fluoxetine (0.1mg/L for 8days) normalized their behavioral and endocrine phenotypes, as well as corrected stress-elevated IL-1β and IL-6 levels, similar to clinical and rodent data. The CNS expression of the bdnf gene, the two genes of its receptors (trkB, p75), and the gfap gene of glia biomarker, the glial fibrillary acidic protein, was unaltered in all three groups. However, PUCS elevated whole-body BDNF levels and the telencephalic dendritic spine density (which were corrected by fluoxetine), thereby somewhat differing from the effects of chronic stress in rodents. Together, these findings support zebrafish as a useful in-vivo model of chronic stress, also calling for further cross-species studies of both shared/overlapping and distinct neurobiological responses to chronic stress.

Animal inflammation-based models of depression and their application to drug discovery.

Abstract: Depression, anxiety and other affective disorders are globally widespread and severely debilitating human brain diseases. Despite their high prevalence and mental health impact, affective pathogenesis is poorly understood, and often remains recurrent and resistant to treatment. The lack of efficient antidepressants and presently limited conceptual innovation necessitate novel approaches and new drug targets in the field of antidepressant therapy. Areas covered: Herein, the authors discuss the emerging role of neuro-immune interactions in affective pathogenesis, which can become useful targets for CNS drug discovery, including modulating neuroinflammatory pathways to alleviate affective pathogenesis. Expert opinion: Mounting evidence implicates microglia, polyunsaturated fatty acids (PUFAs), glucocorticoids and gut microbiota in both inflammation and depression. It is suggested that novel antidepressants can be developed based on targeting microglia-, PUFAs-, glucocorticoid- and gut microbiota-mediated cellular pathways. In addition, the authors call for a wider application of novel model organisms, such as zebrafish, in studying shared, evolutionarily conserved (and therefore, core) neuro-immune mechanisms of depression.

Adult zebrafish in CNS disease modeling: a tank that's half-full, not half-empty, and still filling.

Abstract: The zebrafish (Danio rerio) is increasingly used in a broad array of biomedical studies, from cancer research to drug screening. Zebrafish also represent an emerging model organism for studying complex brain diseases. The number of zebrafish neuroscience studies is exponentially growing, significantly outpacing those conducted with rodents or other model organisms. Yet, there is still a substantial amount of resistance in adopting zebrafish as a first-choice model system. Studies of the repertoire of zebrafish neural and behavioral functions continue to reveal new opportunities for understanding the pathobiology of various CNS deficits. Although some of these models are well established in zebrafish, including models for anxiety, depression, and addiction, others are less recognized, for example, models of autism and obsessive-compulsive states. However, mounting data indicate that a wide spectrum of CNS diseases can be modeled in adult zebrafish. Here, we summarize recent findings using zebrafish CNS assays, discuss model limitations and the existing challenges, as well as outline future directions of research in this field.

Work stress precipitates depression and anxiety in young, working women and men. Commentary

Abstract: Background. Rates of depression have been rising, as have rates of work stress. We tested the influence of work stress on diagnosed depression and anxiety in young working adults. Method. Participants were enrolled in the Dunedin study, a 1972-1973 longitudinal birth cohort assessed most recently in 2004-2005, at age 32 (n=972, 96% of 1015 cohort members still alive). Work stress (psychological job demands, work decision latitude, low work social support, physical work demands) was ascertained by interview. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were ascertained using the Diagnostic Interview Schedule (DIS) and diagnosed according to DSM-IV criteria. Results. Participants exposed to high psychological job demands (excessive workload, extreme time pressures) had a twofold risk of MDD or GAD compared to those with low job demands. Relative risks (RRs) adjusting for all work characteristics were: 1·90 [95% confidence interval (CI) 1·22-2·98] in women, and 2·00 (95 % CI 1·13-3·56) in men. Analyses ruled out the possibility that the association between work stress and disorder resulted from study members' socio-economic position, a personality tendency to report negatively, or a history of psychiatric disorder prior to labour-market entry. Prospective longitudinal analyses showed that high-demand jobs were associated with the onset of new depression and anxiety disorder in individuals without any pre-job history of diagnosis or treatment for either disorder. Conclusions. Work stress appears to precipitate diagnosable depression and anxiety in previously healthy young workers. Helping workers cope with work stress or reducing work stress levels could prevent the occurrence of clinically significant depression and anxiety.

Alarmins and immunity

Abstract: More than a decade has passed since the conceptualization of the "alarmin" hypothesis. The alarmin family has been expanding in terms of both number and the concept. It has recently become clear that alarmins play important roles as initiators and participants in a diverse range of physiological and pathophysiological processes such as host defense, regulation of gene expression, cellular homeostasis, wound healing, inflammation, allergy, autoimmunity, and oncogenesis. Here, we provide a general view on the participation of alarmins in the induction of innate and adaptive immune responses, as well as their contribution to tumor immunity.

Meaning, Medicine, and the “Placebo Effect”

Abstract: Meaning, Medicine, and the “Placebo Effect” Daniel Moerman Cambridge: Cambridge University Press, 2002. xiii. 172 pp.