Clozapine modulation of zebrafish swimming behavior and gene expression as a case study to investigate effects of atypical drugs on aquatic organisms

Gundlach, Michael J.; Paolo, Carolina Di; Chen, Qiqing; Majewski, Kendra; Haigis, Ann-Cathrin; Werner, Inge; Hollert, Henner

doi:10.1016/j.scitotenv.2021.152621

Cited by 5 publications

(3 citation statements)

References 97 publications

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“…Phenylalanine and tyrosine serve as precursors of dopamine, a neurotransmitter associated with reward signaling and pivotal for social and motor behaviors. , Recent research has elucidated the role of dopamine neurons within hypothalamic nuclei in regulating motor behavior . These findings suggested impairment of the dopaminergic system in zebrafish following TCS exposure, aligning with similar observations in response to other environmental contaminants such as perfluorooctanesulfonates and clozapine . Previous studies have suggested that TCS at sublethal concentrations (50–150 μg/L) could induce oxidative stress in various organ of zebrafish, such as brain and liver .…”

Section: Discussionsupporting

confidence: 89%

Insights into Triclosan-Induced Endocrine Disruption: Evidence from the National Health and Nutrition Examination Survey and Zebrafish Models

Li,

Xian,

Ren

et al. 2024

Environ. Health

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Triclosan (TCS) has garnered significant attention due to its widespread use and associated endocrine-disrupting effects. However, its impact on the neuroendocrine system and underlying mechanisms remain poorly understood. Here, we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey (NHANES). Additionally, we investigated TCS's influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS (0.361−48.2 μg/L) for 21 days. Assessment of reproductive and neurotoxicity included histopathological examination and behavioral tests. Transcriptomics, proteomics analyses, and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine disruption. Significant correlations were found between TCS exposure and estradiol, testosterone, and sex hormone-binding globulin levels in NHANES participants. In addition, TCS exposure inhibited ovary development and spermatogenesis in zebrafish. Transcriptomics and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive toxicity. Moreover, TCS exposure induced nervous system impairment, as evidenced by histological changes and altered motor behavior, possibly associated with oxidative damage. Correlation analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS exposure. Overall, this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.

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Section: Discussionsupporting

confidence: 89%

Insights into Triclosan-Induced Endocrine Disruption: Evidence from the National Health and Nutrition Examination Survey and Zebrafish Models

Li,

Xian,

Ren

et al. 2024

Environ. Health

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“…Zebrafish larvae dosed with clozapine were imaged and shown in Figure 5 b (mass spectra from MALDI and DESI are displayed in Figures S3 and S4 , respectively) and serve as an example of our application of a toxicity study model using zebrafish larvae. Clozapine is an atypical antipsychotic [ 22 ], and its effect on zebrafish larvae was reported [ 23 ], hence, it was chosen in the proof-of-concept experiment. The MALDI MS images demonstrated the abundance of clozapine in the brain area and body.…”

Section: Resultsmentioning

confidence: 99%

Optimization of Zebrafish Larvae Sectioning for Mass Spectrometry Imaging

et al. 2022

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The utility of zebrafish is becoming more frequent due to lower costs and high similarities to humans. Zebrafish larvae are attractive subjects for drug screening and drug metabolism research. However, obtaining good quality zebrafish larvae sections for batch samples at designated planes, angles, and locations for comparison purposes is a challenging task. We report here the optimization of fresh frozen zebrafish larvae sectioning for mass spectrometry imaging. We utilized the gelatin solutions that were created at two different temperatures (50 and 85 °C) as embedding media. Gelatin-50 (gelatin created under 50 °C, solid gel under room temperature) was used to make a larvae-shaped mold and gelatin-85 (gelatin created under 85 °C, liquid under room temperature) was used to embed the larvae. H&E staining of sections shows well-preserved morphology and minimal histological interference. More importantly, the position of the larvae was well controlled resulting in more consistent sectioning of the larvae.

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“…Insects send out sexual attractants (pheromones). Other chemicals influence the swarming behavior of fish and grasshoppers [138,139]. Infochemicals play a decisive role in vital processes such as reproduction, social behavior, eating, defense or orientation in most living beings.…”

Section: Endocrine Disruptors and Infochemicalsmentioning

confidence: 99%

The Necessity of a Global Binding Framework for Sustainable Management of Chemicals and Materials—Interactions with Climate and Biodiversity

Steinhäuser¹,

Gleich

Ophoff

et al. 2022

Sustainable Chemistry

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Sustainable chemicals and materials management deals with both the risks and the opportunities of chemicals and products. It is not only focused on hazards and risks of chemicals for human health and the environment but also includes the management of material flows from extraction of raw materials up to waste. It becomes apparent meanwhile that the ever-growing material streams endanger the Earth system. According to a recent publication of Persson et al., the planetary boundaries for chemicals and plastics have already been exceeded. Therefore, sustainable chemicals and materials management must become a third pillar of international sustainability policy. For climate change and biodiversity, binding international agreements already exist. Accordingly, a global chemicals and materials framework convention integrating the current fragmented and non-binding approaches is needed. The impacts of chemicals and materials are closely related to climate change. About one third of greenhouse gas (GHG) emissions are linked to the production of chemicals, materials and products and the growing global transport of goods. Most of it is assigned to the energy demand of production and transport. GHG emissions must be reduced by an expansion of the circular economy, i.e., the use of secondary instead of primary raw materials. The chemical industry is obliged to change its feedstock since chemicals based on mineral oil and natural gas are not sustainable. Climate change in turn has consequences for the fate and effects of substances in the environment. Rising temperature implies higher vapor pressure and may enhance the release of toxicants into the atmosphere. Organisms that are already stressed may react more sensitively when exposed to toxic chemicals. The increasing frequency of extreme weather events may re-mobilize contaminants in river sediments. Increasing chemical and material load also threatens biodiversity, e.g., by the release of toxic chemicals into air, water and soil up to high amounts of waste. Fertilizers and pesticides are damaging the biocoenoses in agrarian landscapes. In order to overcome these fatal developments, sustainable management of chemicals and materials is urgently needed. This includes safe and sustainable chemicals, sustainable chemical production and sustainable materials flow management. All these three sustainability strategies are crucial and complement each other: efficiency, consistency and sufficiency. This obligates drastic changes not only of the quantities of material streams but also of the qualities of chemicals and materials in use. A significant reduction in production volumes is necessary, aiming not only to return to a safe operating space with respect to the planetary boundary for chemicals, plastics and waste but also in order to achieve goals regarding climate and biodiversity.

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Clozapine modulation of zebrafish swimming behavior and gene expression as a case study to investigate effects of atypical drugs on aquatic organisms

Cited by 5 publications

References 97 publications

Insights into Triclosan-Induced Endocrine Disruption: Evidence from the National Health and Nutrition Examination Survey and Zebrafish Models

Insights into Triclosan-Induced Endocrine Disruption: Evidence from the National Health and Nutrition Examination Survey and Zebrafish Models

Optimization of Zebrafish Larvae Sectioning for Mass Spectrometry Imaging

The Necessity of a Global Binding Framework for Sustainable Management of Chemicals and Materials—Interactions with Climate and Biodiversity

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