Dopamine-neurotransmission and nociception in zebrafish: An anti-nociceptive role of dopamine receptor drd2a

Reij, R; Salmans, Maud M.A.; Eijkenboom, Ivo; Hoogen, Nynke J. van den; Joosten, Elbert A.J.; Vanoevelen, Jo

doi:10.1016/j.ejphar.2021.174517

Cited by 6 publications

(5 citation statements)

References 63 publications

(109 reference statements)

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“…A recent study has reported that at 200 μg/L BPAF exhibited the greatest potency of dysregulating dopamine neurotransmitters in comparison with BPA, BPS, and BPF (Gu et al, 2022). Consistent with previous studies (Gu et al, 2022;McPherson et al, 2016;van Reij et al, 2021) reporting the close association of locomotor behavioral abnormalities with dopaminergic signaling in zebrafish, our study indicates that the alterations in zebrafish behavioral responses to BPAF concentrations could be partially attributed to impaired dopaminergic systems. Evidently, the impaired dopaminergic system led to decreased mRNA levels of key genes (pax6a, sox11b, syn2a, and rob2).…”

Section: Discussionsupporting

confidence: 91%

“…The dat gene is crucial in controlling the level of dopamine; overexpression of dat mRNA could result in long-term dysfunction of the developing brain (Bu et al, 2021). The drd2a gene is preferentially expressed in the spinal cord of zebrafish and modulates nociception and controls behavioral alterations (van Reij et al, 2021). Our study detected significant decreased expression of th1 and drd2a and increased expression of dat genes in a BPAF concentration-dependent manner on zebrafish embryonic treatment.…”

Section: Discussionmentioning

confidence: 54%

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Oxidative Stress and Apoptosis in Bisphenol AF–Induced Neurotoxicity in Zebrafish Embryos

Gyimah

Zhu

Zhang

et al. 2022

Enviro Toxic and Chemistry

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Bisphenol AF (BPAF) is a structural counterpart of bisphenol A that is utilized in the food and beverage industry.The present study investigated the potential mechanisms in BPAF-induced neurotoxicity in zebrafish embryos. The BPAF concentrations (0.03, 0.1, 0.3, and 1.0 µM) had no obvious effect on hatching, mortality, and body length of zebrafish larvae, while curved tail and pericardial edema were observed in the 1.0 μM group at 72 and 96 h postfertilization (hpf). Locomotor activity of the larvae (at 120 hpf) significantly decreased from dark to light but increased from light to dark transitions in BPAF groups (0.1, 0.3, and 1.0 μM). Acridine orange showed that BPAF significantly increased green fluorescence protein intensity (22.6%) in the 1.0 μM group. Consistently, the induced apoptosis significantly up-regulated caspase 3 at 0.3 μM (1.95-fold) and 1.0 μM (2.26-fold) and bax at 0.3 μM (1.60-fold) and 1.0 μM (1.78-fold), whereas bcl-2 expression was significantly decreased at 0.3 μM (0.72-fold) and 1.0 μM (0.53-fold). In addition, increased reactive oxygen species concentrations at 0.3 μM (27%) and 1.0 μM (61.4%) resulted in suppressed superoxide dismutase and catalase activities. Moreover, quantitative polymerase chain reaction results showed that BPAF (0.3 and 1.0 μM) significantly altered normal dopaminergic signaling where dat was up-regulated, while drd2a and th1 were down-regulated, in a concentration-dependent manner. Aberrations in dopamine-related genes were congruous with the dysregulations in neurodevelopment genes (sox11b, pax6a, syn2a, and rob2). Our findings suggest that BPAF-evoked oxidative stress and apoptosis could translate into phenotypical behavioral and neurodevelopmental abnormalities. These highlights could provide theoretical reference for risk assessment and act as an early indicator to BPAF exposure.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 54%

Oxidative Stress and Apoptosis in Bisphenol AF–Induced Neurotoxicity in Zebrafish Embryos

Gyimah

Zhu

Zhang

et al. 2022

Enviro Toxic and Chemistry

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“…Several examples of modeling human diseases with PGx-relevant genes in zebrafish already exist, albeit with different research goals. For example, the phenotype conferred by the human rs6277 allele of DRD2 has been successfully modeled in zebrafish using morpholinos against drd2a [ 71 ], and zebrafish models of neurodegeneration are being employed to identify mechanisms and treatments for Parkinson’s disease [ 72 ]. Another gene included in our tiered pharmacogene list that has high sequence conservation and was found to be expressed at 3- and 5-dpf is the gene encoding the mitochondrial 12s rRNA subunit, mt-rnr1 .…”

Section: Discussionmentioning

confidence: 99%

Identification, conservation, and expression of tiered pharmacogenes in zebrafish

Demery-Poulos

Chambers

2022

PLoS ONE

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The number of adverse drug events in the United States is critically high, with annual rates exceeding 1 million cases over the last nine years. One cause of adverse drug events is the underlying genetic variation that can alter drug responses. Pharmacogenomics is a growing field that seeks to better understand the relationship between a patient’s genetics and drug efficacy. Currently, pharmacogenomics relies largely on human trials, as there is not a well-developed animal model for studying preventative measures and alternative treatments. Here, we analyzed pharmacogene expression at two developmental time points in zebrafish to demonstrate the potential of using this model organism for high-throughput pharmacogenomics research. We found that 76% of tiered human pharmacogenes have a zebrafish ortholog, and of these, many have highly conserved amino acid sequences. Additional gene ontology analysis was used to classify pharmacogenes and identify candidate pathways for future modeling in zebrafish. As precision medicine burgeons, adopting a high-throughput in vivo model such as the zebrafish could greatly increase our understanding of the molecular pathology underlying adverse drug events.

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“…Simultaneously, healthy zebrafish were exposed to Halo (8 μM) as a negative control and Quin (4 μM) as a positive control for 7 days. The levels of Quin and Halo were chosen based on previous studies and our preliminary experiment results, which demonstrate that 8 μM haloperidol or 4 μM quinpirole may significantly change the expression of drd2b but does not affect the normal growth of zebrafish. – …”

Section: Methodsmentioning

confidence: 99%

2-Ethylhexyl Diphenyl Phosphate Causes Obesity in Zebrafish by Stimulating Overeating via Inhibition of Dopamine Receptor D2

Yang,

Zhang,

Deng

et al. 2023

Environ. Sci. Technol.

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Obesity is a popular public health problem worldwide and is mainly caused by overeating, but little is known about the impacts of synthetic chemicals on obesity. Herein, we evaluated the obesogenic effect caused by 2-ethylhexyl diphenyl phosphate (EHDPHP) on zebrafish. Adult zebrafish were exposed to 5, 35, and 245 μg/L of EHDPHP for 21 days. Results showed that EHDPHP exposure significantly promoted the feeding behavior of zebrafish, as evidenced by shorter reaction time, increased average food intake, feeding rate, and intake frequency (p < 0.05). Transcriptomic, real-time quantitative PCR, and neurotransmitter analyses revealed that the dopamine (DA) receptor D2 (DRD2) was inhibited, which interfered with the DA neural reward regulation system, thus stimulating food addiction to zebrafish. This was further verified by the restored DRD2 after 7 days of Halo (a DRD2 agonist) treatment. A strong interaction between EHDPHP and DRD2 was identified via molecular docking. As a consequence of the abnormal feeding behavior, the exposed fish exhibited significant obesity evidenced by increased body weight, body mass index, plasma total cholesterol, triglyceride, and body fat content. Additionally, the pathways linked to Parkinson’s disease, alcoholism, and cocaine addiction were also disrupted, implying that EHDPHP might cause other neurological disorders via the disrupted DA system.

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Dopamine-neurotransmission and nociception in zebrafish: An anti-nociceptive role of dopamine receptor drd2a

Cited by 6 publications

References 63 publications

Oxidative Stress and Apoptosis in Bisphenol AF–Induced Neurotoxicity in Zebrafish Embryos

Oxidative Stress and Apoptosis in Bisphenol AF–Induced Neurotoxicity in Zebrafish Embryos

Identification, conservation, and expression of tiered pharmacogenes in zebrafish

2-Ethylhexyl Diphenyl Phosphate Causes Obesity in Zebrafish by Stimulating Overeating via Inhibition of Dopamine Receptor D2

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