Gene-class analysis of expression patterns induced by psychoactive pharmaceutical exposure in fathead minnow (Pimephales promelas) indicates induction of neuronal systems

Abstract

Psychoactive pharmaceuticals are among the most frequently prescribed drugs, contributing to persistent measurable concentrations in aquatic systems. Typically, it is assumed that such contaminants have no human health implications because they exist in extremely low concentrations. We exposed juvenile fathead minnows (Pimephales promelas) to three pharmaceuticals, fluoxetine, venlafaxine and carbamazepine, individually and in a mixture, and measured their effect on the induction of gene expression in fish brains using microarray analysis. Gene expression changes were accompanied by behavioral changes and validated by qPCR analysis. Gene Set Enrichment Analysis was used to perform gene-class analysis of gene expression, testing for enrichment of gene sets known to be involved in human neuronal development, regulation and growth. We found significant enrichment of gene sets for each of the treatments, with the largest induction of expression by the mixture treatment. These results suggest that the psychoactive pharmaceuticals are able to alter expression of fish genes associated with development, regulation and differentiation of synapses, neurons and neurotransmitters. The results provide a new perspective for the consideration of potential consequence for human health due to environmental exposure to unmetabolized psychoactive pharmaceuticals.

Physiological and Ethological Effects of Fluoxetine, A Study Using Ants as Biological Models

“…7, No. 2;2015 ants will examine effects of antidepressants free of fluoxetine, for checking if these effects (somewhat reported by Brodin, Fick, Jonsson &Klaminder, 2013 andThomas, Joshi &Klaper, 2012) are weaker than those of antidepressants containing fluoxetine, and if physical dependence to them occurs. Let us recall that, in the course of the present experimentation, ants never develop habituation to or dependence on fluoxetine consumption.…”

Reprint of: Effects of the antidepressant venlafaxine on fish brain serotonin and predation behavior

“…Serotonin may also influence appetite and behavior through modulation of downstream processes including controlling the release of various hormones in fish responsible for regulating growth, stress response, behavior, and reproductive function (Somoza and Peter, 1991;Medeiros et al, 2010;Overli et al, 1999;Winberg and Lepage, 1998;Lowry and Moore, 2006). More specifically, venlafaxine has been shown to decrease egg production in zebra fish (Galus et al, 2013;Mennigen et al, 2009), cause up-regulation of genes indicative of neurodegredation and modulation of action potentials in fathead minnow brains (Thomas et al, 2012), and inhibit both basal and epinephrine induced glucose production in rainbow trout hepatocytes (Ings et al, 2012) which may result in decreased brain serotonin in fish (Ruibal et al, 2002) Behavioral results from this study indicated that venlafaxine has less of an effect than fluoxetine. Fluoxetine concentrations as low as 23 g/L were shown to cause significant reduction in the ability of hybrid striped bass to capture prey 1, 2, and 3 (Gaworecki and Klaine, 2008) while the lowest concentration tested in the current study (35 g/L) only caused a significant effect on the time to capture prey 3.…”

“…Venlafaxine has been shown to block epinephrine induced glucose production in rainbow trout (Oncorhynchus mykiss) hepatocytes which may have implications for stress response in exposed fish (Ings et al, 2012). Though uptake of venlafaxine into fish neural tissue has been shown to be limited during environmentally relevant exposures (Schultz et al, 2010;Schultz et al, 2011) gene expression patterns in the brains of fathead minnows exposed to venlafaxine reveal upregulation of genes related to neural development and regulation of action potentials (Thomas et al, 2012). But researchers have yet to examine the targeted outcome of venlafaxine, modulation of serotonin.…”

Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations

“…These synthetic chemicals may serve as environmental factors that act as a trigger in genetically susceptible individuals [7, 9–12]. Our study focused on a specific class of potential toxicants, pharmaceuticals and personal care products (PPCP) [13]. PPCPs mainly involved psychoactive pharmaceuticals, which have been detected in the drinking water at low concentrations [14, 15].…”

“…Psychoactive pharmaceuticals are among the most highly prescribed classes of drug in United States [13, 14, 16] and patient excretions still contain active metabolites that have considerably long half-lives [14, 17]. Waste-water treatment plants release PPCP-contaminated water into surface water such as rivers and lakes [17].…”