Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

Abstract

Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.

Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance

“…7A). These results replicate and reinforce previous studies showing that UCS induces anxiety-like behavior in zebrafish (Chakravarty et al, 2013; Demin et al, 2020; Marcon et al, 2019, 2018a, 2016; Mocelin et al, 2019; O’Daniel and Petrunich-Rutherford, 2020; Piato et al, 2011; Reddy et al, 2021; Song et al, 2018). Both CUR and MC were unable to block these alterations.…”

“…The unpredictable chronic stress induces several behavioral and neurochemical characteristics that resemble those observed in patients with anxiety and/or mood disorders (Chattarji et al, 2015; Willner, 2017, 2005). Antidepressants (Demin et al, 2020; Marcon et al, 2016; Reddy et al, 2021; Song et al, 2018), anxiolytics (Marcon et al, 2016), antioxidant (Marcon et al, 2019; Mocelin et al, 2019), ketamine (Reddy et al, 2021) and prazosin (O’Daniel and Petrunich-Rutherford, 2020) showed protective effects in this model.…”

Effects of chronic exposure to fluoxetine, eicosapentaenoic acid, and lipopolysaccharide on behavior and hippocampal transcriptome in the rat model of prolonged chronic unpredictable stress

“…Comparing our present rat PCUS results with mouse data in a different, social defeat-based chronic stress model, 153 , we note that both stressors reduce hippocampal expression of Dedicator Of Cytokinesis 10 ( Dock10 ), a poorly studied immune gene 154 . Cardiac muscle troponin T ( Tnnt2 ) orthologues ( Tnnt2 and tnnt2a ), parts of the troponin complex, were both upregulated in PCUS rats and in zebrafish subjected to 5-week PCUS 74 . However, novel data mining tools are needed to target species-specific and cross-species data, also aiming to identify evolutionarily conserved core aspects that may be used to better compare and interpret animal data.…”

“…Brain samples for transcriptomic analyses were collected without pooling (1 brain per sample) one day after the last behavioral test, between 9:00 and 19.00. The 1-day interval was used here to minimize concomitant immediate genomic effects of behavioral testing and/or handling 74 . Rats (n=3) for RNA-sequencing analysis were chosen from the groups using a random number generator (https://www.random.org/).…”

Behavioral and neurochemical effects of novel N-Benzyl-2-phenylethylamine derivatives in adult zebrafish

“…Since brain monoaminergic systems play a key role in NBOMe CNS effects 31–37 , here we studied changes in zebrafish whole-brain concentrations of norepinephrine (NE), serotonin (5-HT), dopamine (DA) and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) using the high-performance liquid chromatography (HPLC), similarly to 73, 74, 77, 96, 102, 103 . As in the NTT and ZTI studies, fish (n=7-10) were pre-exposed to 20 mg/L of 24H-NBF, 34H-NBOMe, 34H-NBF, 34H-NBCl, 34H-NBBr, 34H-NBOMe, or to 10 mg/L 24H-NBBr, 24H-NBOMe(F) or drug-free water, in the 0.5L beaker for 20 min.…”