Adverse effects of serotonin depletion in developing zebrafish

Airhart, Mark J.; Lee, Deborah H.; Wilson, Tracy D.; Miller, Barney E.; Miller, Merry N.; Skalko, Richard G.; Monaco, Paul J.

doi:10.1016/j.ntt.2011.08.008

Cited by 51 publications

(41 citation statements)

References 43 publications

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“…No significant changes were observed for short incubation times. While obvious developmental malformations and defects were not observed in this study with the exposure levels studied, higher internalization of nanoceria and longer exposure times could potentially result in further 5-HT depletion and might affect body length, locomotor behavior and serotonin message related expression 52 .…”

Section: Discussioncontrasting

confidence: 56%

Effect of cerium oxide nanoparticles on intestinal serotonin in zebrafish

et al. 2013

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Cerium oxide nanoparticles or nanoceria are emerging as a new and promising class of nanoparticle technology for biomedical applications. The safe implementation of these particles in clinical applications requires evaluation of their redox properties and reactivity that might cause neurotoxic effects by interacting with redox components of the physiological environment. We report in vitro and in vivo studies to evaluate the impact of nanoceria exposure on serotonin (5-HT), an important neurotransmitter that plays a critical role in various physiological processes including motility and secretion in the digestive system. In vitro studies of 5-HT in the presence of nanoceria using spectroscopic, electrochemical and surface characterization methods demonstrate that nanoceria interacts with 5-HT and forms a surface adsorbed 5-HT-nanoceria complex. Further in vivo studies in live zebrafish embryos indicate depletion of the 5-HT level in the intestine for exposure periods longer than three days. Intestinal 5-HT was assessed quantitatively in live embryos using implantable carbon fiber microelectrodes and the results were compared to immunohistochemistry of the dissected intestine. 20 and 50 ppm nanoparticle exposure decreased the 5-HT level to 20.5 (±1.3) and 5.3 (±1.5) nM respectively as compared to 30.8 (±3.4) nM for unexposed control embryos. The results suggest that internalized nanoceria particles can concentrate 5-HT at the nanoparticle accumulation site depleting it from the surrounding tissue. This finding might have long term implications in the neurophysiology and functional development of organisms exposed to these particles through intended or unintended exposure.

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Section: Discussioncontrasting

confidence: 56%

Effect of cerium oxide nanoparticles on intestinal serotonin in zebrafish

et al. 2013

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“…Thus, inhibited transcription levels of tph1 , tph2 and tphr suggested reduced synthesis of 5‐HT, and this may explain the decreased 5‐HT levels in zebrafish larvae exposed to PBDEs. In a previous study, embryonic exposure to p‐chlorophenylalanine, an inhibitor of TPH, resulted in decreased transcripts of htr1a in the brain and spinal cord, and in reduced SERT in the spinal cord of zebrafish (Airhart et al ., ). Similarly, the gene transcripts of htr1aa/b and serta / b were also found to be inhibited in addition to the decreased tph transcripts in DE‐71‐exposed zebrafish larvae.…”

Section: Discussionmentioning

confidence: 97%

“…Although the specific role of the serotonergic system in the control of behavior is not clear, some correlations between the locomotion and 5‐HT levels have been established. For example, 5‐HT‐depleted mice exhibited hypoactivity in spontaneous locomotor activity and a less anxious performance in light–dark box exploration, and in zebrafish, serotonin depletion resulted in significantly less movement (Airhart et al ., ; Schaefer et al ., ), which is similar to the behavioral observations in our study. Thus, our results indicate that the behavioral changes of zebrafish larvae upon PBDE exposure were related, at least partially, to the decreased 5‐HT levels.…”

Section: Discussionmentioning

confidence: 99%

The neurotoxicity of DE‐71: effects on neural development and impairment of serotonergic signaling in zebrafish larvae

Wang

Yang

Wang

et al. 2016

J of Applied Toxicology

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The underlying mechanism of polybrominated diphenyl ether (PBDE)-induced neurotoxicity is still a major concern due to its ubiquitous nature and persistence. Here, zebrafish embryos (2 h postfertilization, hpf ) were exposed to different concentrations of the commercial PBDE mixture DE-71 (0-100 μg l -1 ) until 120 hpf, and the impact on neural development and serotonergic system was investigated. The in vivo results revealed significantly reduced transcription of genes involved in neurogenesis (fgf8, shha, wnt1), and contents of proteins in neuronal morphogenesis (myelin basic protein, synapsin IIa), suggesting an impairment of neural development in zebrafish embryos. Further results demonstrated a reduction of 5-hydroxytryptamine neuron and a dose-dependent decrease of whole-body serotonin levels, as well as the transcription of genes involved in serotonergic synthesis (tph1, tph2, trhr) and neurotransmission (serta/b, htr1aa/b). In addition, we predicted possible targets of PBDEs by molecular docking, and the results indicated that PBDE congeners showed high binding affinities with fibroblast growth factor 8 other than SHH and HTR1B. Taken together, this study demonstrated that PBDE exposure during embryogenesis could damage neural development and cause impairment of the serotonergic system as secondary effects in the zebrafish larvae.

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“…Studies in zebrafish embryos demonstrate that aqueous fluoxetine exposure changed not only SERT but also 5-HT 1A receptor function with detrimental effects on locomotion and the nervous system (Airhart et al 2007; Airhart et al 2012). This area deserves more attention, given the advent of multimodal SERT and 5-HT 1A targeting drugs.…”

Section: Discussionmentioning

confidence: 99%

Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments

Connors

Valenti²,

Lawless

et al. 2014

Aquatic Toxicology

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The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitolizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [3H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of simalarly Gαi/o-coupled cannabinoid receptors. [3H] 8-OH-DPAT specific binding was 176 ± 8, 275 ± 32, and 230 ± 36 fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [3H] WIN55,212-2 binding density was higher in those same brain regions at 6 ± 0.3, 5.5 ± 0.4 and 7.3 ± 0.3 pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50 mg/L), or dietary exposure to WIN55,212-2 (7 μg/week) zebrafish spent more time in and/or entered white arms more often than controls (p < 0.05). Acute exposure to WIN55,212-2 at 0.5-50 mg/L, reduced mobility. These behavioral findings suggest that azipirones, like cannabinoid agonists, have anxiolytic and/or sedative properties on fish in novel environments. These observations highlight the need to consider potential ecological risks of azapirones and multimodal antidepressants in the future.

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Adverse effects of serotonin depletion in developing zebrafish

Cited by 51 publications

References 43 publications

Effect of cerium oxide nanoparticles on intestinal serotonin in zebrafish

Effect of cerium oxide nanoparticles on intestinal serotonin in zebrafish

The neurotoxicity of DE‐71: effects on neural development and impairment of serotonergic signaling in zebrafish larvae

Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments

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