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Slidell, LA, United States

Stewart A.M.,University of Illinois at Chicago | Kalueff A.V.,Tulane University | Kalueff A.V.,ZENEREI Institute
Current Neuropharmacology | Year: 2012

Whereas cognitive impairment is a common symptom in multiple brain disorders, predictive and highthroughput animal models of cognition and behavior are becoming increasingly important in the field of translational neuroscience research. In particular, reliable models of the cognitive deficits characteristic of numerous neurobehavioral disorders such as Alzheimer's disease and schizophrenia have become a significant focus of investigation. While rodents have traditionally been used to study cognitive phenotypes, zebrafish (Danio rerio) are gaining popularity as an excellent model to complement current translational neuroscience research. Here we discuss recent advances in pharmacological and genetic approaches using zebrafish models to study cognitive impairments and to discover novel cognitive enhancers and neuroprotective mechanisms. © 2012 Bentham Science Publishers.

Stewart A.M.,ZENEREI Institute | Stewart A.M.,Tulane University | Roy S.,Tulane University | Wong K.,Tulane University | And 4 more authors.
Behavioural Brain Research | Year: 2015

Mounting clinical and experimental evidence implicates various cytokines in stress-related affective brain disorders. Here, we analyze behavioral phenotypes in C57BL/6J male mice following the chronic social defeat stress paradigm, and examine their serum cytokines and corticosterone levels. Loser mice experiencing 20 days of daily 15-min social confrontations demonstrate elevated levels of pro-inflammatory cytokines interleukin IL-7 and vascular endothelial growth factor (VEGF), as well as a trend to increase IL-6 and IL-15. We also found higher levels of an anti-inflammatory cytokine IL-10 in the winner mice, with unaltered serum IL-2, IL-4, IL-1a, MCP-1 and corticosterone levels between the groups. Overall, our results suggest that animal affective-like states correlate with specific cytokine profiles, including some cytokines (e.g., VEGF, IL-7 or IL-15) whose role in neuropsychiatric disorders is only beginning to emerge. This study emphasizes the importance of integrative analyses of neural and immune phenotypes in stress and stress-related neurobehavioral disorders. These findings may also help foster the search for new therapeutic and preventative strategies that target selected cytokines and their signaling pathways. © 2014 Elsevier B.V.

Stewart A.M.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | Kalueff A.V.,ZENEREI Institute | Kalueff A.V.,Tulane University
Brain Research | Year: 2014

The use of psychotropic drugs in clinical and translational brain research continues to grow, and the need for novel experimental models and screens is becoming widely recognized. Mounting evidence supports the utility of zebrafish (Danio rerio) for studying various pharmacological manipulations, as an alternative model complementing the existing rodent paradigms in this field. Here, we explore the effects of acute 20-min exposure to two commonly abused psychotropic compounds, Δ9-tetrahydrocannabinol (THC) and heroin, on adult zebrafish behavior in the novel tank test. Overall, THC administration (30 and 50 mg/L) produces an anxiogenic-like reduction of top swimming, paralleled with a slower, continuous bottom swimming. In contrast, heroin exposure (15 and 25 mg/L) evoked a hyperlocomotor response (with rapid bouts of bottom swimming and frequent 'bouncing' motions) without altering anxiety-sensitive top/bottom endpoints. The behavioral effects of these two compounds in zebrafish seem to parallel the respective rodent and human findings. Collectively, this emphasizes the growing significance of novel emerging aquatic models in translational drug abuse research and small molecule screening. © 2013 Elsevier B.V.

Stewart A.M.,ZENEREI Institute | Stewart A.M.,International Zebrafish Neuroscience Research Consortium ZNRC | Ullmann J.F.P.,International Zebrafish Neuroscience Research Consortium ZNRC | Ullmann J.F.P.,University of Queensland | And 8 more authors.
Molecular Psychiatry | Year: 2015

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research. © 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15.

Nguyen M.,University of Virginia | Nguyen M.,ZENEREI Institute | Roth A.,Texas Tech University Health Sciences Center | Kyzar E.J.,University of Illinois at Chicago | And 5 more authors.
Neurochemistry International | Year: 2014

Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca2+ signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis. © 2014 Elsevier Ltd. All rights reserved.

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