Biology subjects

Strekalova, T.

Publications and source records attributed to Strekalova, T..

3 recordsLinked to original sources

bioRxiv2022

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

Serotonergic hallucinogenic drugs potently affect human brain and behavior, and have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing rodent studies, zebrafish (Danio rerio) is a powerful animal model for screening neuroactive drugs, including serotonergic agents. Here, we test ten different 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 phenyl ring of N-benzyl fragment, assessing their behavioral and neurochemical effects in adult zebrafish. Overall, substitutions in N-benzyl fragment primarily affected zebrafish locomotion, and in phenethylamine moiety - anxiety-like behavior, also modulating brain serotonin and/or dopamine turnover. We also identified several behavioral clusters, 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)) agents. The 24H-NBOMe(F) and 34H-NBOMe(F) also reduced despair-like behavior in zebrafish. The artificial intelligence-driven phenotyping supports association of multiple compounds with NMDA antagonists and/or MDMA, supporting their potential hallucinogenic-like properties, as well as other valuable psychoactive effects. In silico functional molecular activity modelling also supports existing of similarities between studied NBPEAs drugs, MDMA, and ketamine. Functional analysis implicates potential involvement of serotonin release stimulating activity, calcium channel (voltage-sensitive) activity, some serotonin receptors activity and variety of psychiatric and neurologic disorders treatments activities. Overall, we report potent neuroactive properties of several novel synthetic N-benzylphenylethylamines in an in vivo vertebrate model system (zebrafish), raising the possibility of their potential use in clinical practice.

neuroscience↗

bioRxiv2021

Modulation of behavioral and hippocampal transcriptomic responses in rat prolonged chronic unpredictable stress model by fluoxetine, eicosapentaenoic acid and lipopolysaccharide

Animal models are widely used to study stress-induced affective disorders and associated with them neuroinflammation and other neuroimmune processes. Here, we examined rat behavioral and hippocampal transcriptomic responses to prolonged chronic unpredictable stress (PCUS), as well as following a 4-week treatment with a classical antidepressant fluoxetine, an anti-inflammatory agent eicosapentaenoic acid (EPA), a pro-inflammatory agent lipopolysaccharide (LPS) and their combinations. Overall, PCUS evoked an anxiety-like behavioral phenotype in rats (corrected by chronic fluoxetine alone or combined with other drugs), EPA was anxiolytic and LPS promoted anxiety in this model. PCUS evoked pronounced transcriptomic responses in rat hippocampi, including >200 differentially expressed genes. While pharmacological manipulations did not affect hippocampal gene expression markedly, Gpr6, Drd2 and Adora2a were downregulated in stressed rats treated with fluoxetine+EPA, suggesting G protein-coupled receptor 6, dopamine D2 receptor and adenosine A2A receptor as potential evolutionarily conserved targets in chronic stress. Overall, these findings support the validity of rat PCUS paradigm as a useful tool to study stress-related affective pathologies and calls for further research probing how various conventional and novel drugs modulate behavioral and neurotranscriptomic biomarkers of chronic stress.

neuroscience↗

bioRxiv2019

Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

genetics↗