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Effects of low-dose methylcyclopentadienyl manganese tricarbonyl-derived manganese on the development of diencephalic dopaminergic neurons in zebrafish
2021
Fasano, Giulia | Godoy, Rafael Soares | Angiulli, Elisa | Consalvo, Ada | Franco, Cristina | Mancini, Maria | Santucci, Daniela | Alleva, E. (Enrico) | Ciavardelli, Domenico | Toni, Mattia | Biffali, Elio | Ekker, Marc | Canzoniero, Lorella Maria Teresa | Sordino, Paolo
Fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) is counted as an organic manganese (Mn)-derived compound. The toxic effects of Mn (alone and complexed) on dopaminergic (DA) neurotransmission have been investigated in both cellular and animal models. However, the impact of environmentally relevant Mn exposure on DA neurodevelopment is rather poorly understood. In the present study, the MMT dose of 100 μM (about 5 mg Mn/L) caused up-regulation of DA-related genes in association with cell body swelling and increase in the number of DA neurons of the ventral diencephalon subpopulation DC2. Furthermore, our analysis identified significant brain Mn bioaccumulation and enhancement of total dopamine levels in association with locomotor hyperactivity. Although DA levels were restored at adulthood, we observed a deficit in the acquisition and consolidation of memory. Collectively, these findings suggest that developmental exposure to low-level MMT-derived Mn is responsible for the selective alteration of diencephalic DA neurons and with long-lasting effects on fish explorative behaviour in adulthood.
Show more [+] Less [-]Environmental co-exposure to TBT and Cd caused neurotoxicity and thyroid endocrine disruption in zebrafish, a three-generation study in a simulated environment
2020
Li, Ping | Li, Zhi-Hua
Although the coexistence of heavy metals and environmental hormones always occur in aquatic environment, the information of the combined impacts remains unclear. To explore the multi-generational toxicity of cadmium (Cd) and tributyltin (TBT), adult zebrafish (Danio rerio) (F0) were exposed to different treated groups (100 ng/l Cd, 100 ng/l TBT and their mixture) for 90 d, with their offspring (F1 and F2) subsequently reared in the same exposure solutions corresponding to their parents. Both developmental neurotoxicity and thyroid disturbances were examined in the three (F0, F1, and F2) generations. Our results showed that co-exposure to Cd and TBT induced the developmental neurotoxicity in F1 and F2 generations, reflected by the significant lower levels of neurotransmitters (dopamine and serotonin) and the inhibited acetylcholinesterase (AChE) activities. And the thyroid endocrine disruption were observed in the two-generations larval offspring by parental exposure to Cd and/or TBT, including the significantly decreasing levels of thyroid hormones and the down-regulated the expression of genes involved in the hypothalamus-pituitary-thyroid axis, compared to the control. Additional, the embryonic toxicity and growth inhibition were also determined in the fish larvae. Overall, this study examined the impacts of parental co-exposure to Cd and TBT, with regard to developmental inhibition, nervous system damage and endocrine disruption, which highlighted that co-exposure influences are complicated and need to be considered for accurate environmental risk assessment.
Show more [+] Less [-]Dopamine alleviates bisphenol A-induced phytotoxicity by enhancing antioxidant and detoxification potential in cucumber
2020
Ahammed, Golam Jalal | Wang, Yaqi | Mao, Qi | Wu, Meijuan | Yan, Yaru | Ren, Jingjing | Wang, Xiaojuan | Liu, Airong | Chen, Shuangchen
Bisphenol A (BPA) is an emerging organic pollutant, widely distributed in environment. Plants can uptake and metabolize BPA, but BPA accumulation induces phytotoxicity. In this study, we administered dopamine, a kind of catecholamines with strong antioxidative potential, to unveil its role in cucumber tolerance to BPA stress. The results showed that exposure to BPA (20 mg L⁻¹) for 21 days significantly reduced growth and biomass accumulation in cucumber seedlings as revealed by decreased lengths and dry weights of shoots and roots. While BPA exposure decreased the chlorophyll content, cell viability and root activity, it remarkably increased reactive oxygen species (ROS) accumulation, electrolyte leakage and malondialdehyde (MDA) content, suggesting that BPA induced oxidative stress in cucumber. However, exogenous dopamine application significantly improved the photosynthetic pigment content, root cell viability, growth and biomass accumulation, and decreased the ROS and MDA levels by increasing the activity of antioxidant enzymes under BPA stress. Further analysis revealed that dopamine application significantly increased the glutathione content and the transcripts and activity of glutathione S-transferase under co-administration of dopamine and BPA compared with only BPA treatment. Moreover, dopamine decreased the BPA content in both leaves and roots, suggesting that dopamine promoted BPA metabolism by enhancing the glutathione-dependent detoxification. Our results show that dopamine has a positive role against BPA phytotoxicity and it may reduce the risks-associated with the dietary intake of BPA through consumption of vegetables.
Show more [+] Less [-]Butylated hydroxytoluene induces hyperactivity and alters dopamine-related gene expression in larval zebrafish (Danio rerio)
2020
Liang, Xue-fang | Zhao, Yaqian | Liu, Wang | Li, Zhitong | Souders, Christopher L. | Martyniuk, Christopher J.
Butylated hydroxytoluene (BHT) is one of the most frequently used synthetic phenolic antioxidants added to food and consumer products such as plastics as a preservative. Due to its high production volume, BHT has been detected in aquatic environments, raising concerns about sub-lethal toxicity. However, there are limited toxicological data for BHT, especially in fish. In this study, zebrafish embryos were exposed to BHT at concentrations ranging 0.01–100 μM for up to 6 days post fertilization (dpf). Acute toxicity was assessed, and experiments revealed that BHT had a 96 h LC50 value of 57.61 μM. At sub-lethal doses (0.1–60 μM), BHT markedly decreased heart rates of zebrafish embryos at 48 h and 72 h by ∼25–30%. Basal and maximal respiration of zebrafish embryos at 24 hpf were decreased by 59.3% and 41.4% respectively following exposure to 100 μM BHT. Behavior in zebrafish was measured at 6 dpf following exposures to 0.01–10 μM BHT. Locomotor behaviors (e.g. total distance moved and velocity) were significantly increased in larvae at doses higher than 0.1 μM BHT. In addition, dark-avoidance behavior was decreased following exposure to 0.01 μM BHT, while conversely, it was increased in zebrafish exposed to 0.1 μM BHT. To investigate potential underlying mechanisms that could explain behavioral changes, transcripts involved in dopamine signaling were measured. Relative expression of dat mRNA was increased in larval fish from the 0.01 μM BHT treatment, while there were no effects on dat mRNA levels at higher concentrations. The mRNA levels of drd3 were decreased in zebrafish from the 1 μM BHT treatment. Taken together, BHT can affect the expression of the dopamine system, which is hypothesized to be related to the abnormal anxiety-associated behavior of larval zebrafish.
Show more [+] Less [-]Perfluorododecanoic acid exposure induced developmental neurotoxicity in zebrafish embryos
2018
Guo, Xiaochun | Zhang, Shengnan | Lu, Shaoyong | Zheng, Binghui | Xie, Ping | Chen, Jun | Li, Guangyu | Liu, Chunsheng | Wu, Qin | Cheng, Houcheng | Sang, Nan
Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6 mg/L PFDoA for 120 h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6 mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6 mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system.
Show more [+] Less [-]Obesogenic effect of erythromycin on Caenorhabditis elegans through over-eating and lipid metabolism disturbances
2022
Luo, Zhili | Yu, Zhenyang | Yin, Daqiang
Environmental obesogens contributed significantly to the obesity prevalence. Recently, antibiotics joined the list of environmental obesogens, while the underlying mechanisms remained to be explored. In the present study, effects of erythromycin (ERY), one widely used macrolide antibiotic, were measured on C. elegans to investigate the obesogenic mechanism. Results showed that ERY at 0.1 μg/L significantly increased the fat content by 17.4% more than the control and also stimulated triacylglycerol (TAG) levels by 25.7% more than the control. Regarding the obesogenic mechanisms, ERY provoked over-eating by stimulation on the pharyngeal pumping and reduction on the satiety quiescence percentage and duration. Such effects were resulted from stimulation on the neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh). The nervous responses involved the up-regulation of Gsα (e.g., ser-7, gsa-1, acy-1 and kin-2) signaling pathway and the down-regulation of TGFβ (daf-7) but not via cGMP-dependent regulations (e.g., egl-4). Moreover, ERY stimulated the activities of fatty acid synthase (FAS) and glycerol-3-phosphateacyl transferases (GPAT) that catalyze lipogenesis, while ERY inhibited those of acyl-CoA synthetase (ACS), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) that catalyze lipolysis. The unbalance between lipogenesis and lipolysis resulted in the fat accumulation which was consistent with up-regulation on mgl-1 and mgl-3 which are the down-steam of TGFβ regulation. Such consistence supported the close connection between nervous regulation and lipid metabolism. In addition, ERY also disturbed insulin which connects lipid with glucose in metabolism.
Show more [+] Less [-]Night melatonin levels affect cognition in diurnal animals: Molecular insights from a corvid exposed to an illuminated night environment
2022
Buniyaadi, Amaan | Prabhat, Abhilash | Bhardwaj, Sanjay Kumar | Kumar, Vinod
This study investigated the role of nocturnal melatonin secretion in the cognitive performance of diurnal animals. An initial experiment measured the cognitive performance in Indian house crows treated for 11 days with 12 h light at 1.426 W/m² (∼150 lux) coupled with 12 h of 0.058 W/m² (∼6-lux) dim light at night (dLAN) or with absolute darkness (0 lux dark night, LD). dLAN treatment significantly decreased midnight melatonin levels and negatively impacted cognitive performance. Subsequently, the role of exogenous melatonin (50 μg; administered intraperitoneally half an hour before the night began) was assessed on the regulation of cognitive performance in two separate experimental cohorts of crows kept under dLAN; LD controls received vehicle. Exogenous melatonin restored its mid-night levels under dLAN at par with those under LD controls, and improved the cognitive performance, as measured in the innovative problem-solving, and spatial and pattern learning-memory efficiency tests in dLAN-treated crows. There were concurrent molecular changes in the cognition-associated brain areas, namely the hippocampus, nidopallium caudolaterale and midbrain. In particular, the expression levels of genes involved in neurogenesis and synaptic plasticity (bdnf, dcx, egr1, creb), and dopamine synthesis and signalling (th, drd1, drd2, darpp32, taar1) were restored to LD control levels in crows treated with illuminated nights and received melatonin. These results demonstrate that the maintenance of nocturnal melatonin levels is crucial for an optimal higher-order brain function in diurnal animals in the face of an environmental threat, such as light pollution.
Show more [+] Less [-]Environmental exposure to 17β-trenbolone during adolescence inhibits social interaction in male mice
2021
Zhang, Shaozhi | Jiao, Zihao | Zhao, Xin | Sun, Mingzhu | Feng, Xizeng
Puberty is a critical period for growth and development. This period is sensitive to external stimuli, which ultimately affects the development of nerves and the formation of social behaviour. 17β-Trenbolone (17β-TBOH) is an endocrine disrupting chemicals (EDCs), which had been widely reported in aquatic vertebrates. But there is little known about the effects of 17β-TBOH on mammals, especially on adolescent neurodevelopment. In this study, we found that 17β-TBOH acute 1 h exposure can cause the activation of the dopamine circuit in pubertal male balb/c mice. At present, there is little known about the effects of puberty exposure of endocrine disruptors on these neurons/nerve pathways. Through a series of behavioural tests, exposure to 80 μgkg⁻¹ d⁻¹ of 17β-TBOH during adolescence increased the anxiety-like behaviour of mice and reduced the control of wheel-running behaviour and the response of social interaction behaviour. The results of TH immunofluorescence staining showed that exposure to 17β-TBOH reduced dopamine axon growth in the medial prefrontal cortex (mPFC). In addition, the results of real-time PCR showed that exposure to 17β-TBOH not only down-regulated the expression of dopamine axon development genes, but also affected the balance of excitatory/inhibitory signals in mPFC. In this research, we reveal the effects of 17β-TBOH exposure during adolescence on mammalian behaviour and neurodevelopment, and provide a reference for studying the origin of adolescent diseases.
Show more [+] Less [-]Parental exposure to environmental concentrations of tris(1,3-dichloro-2-propyl)phosphate induces abnormal DNA methylation and behavioral changes in F1 zebrafish larvae
2020
Ding, Xisheng | Sun, Wen | Dai, Lili | Liu, Chunsheng | Sun, Qian | Wang, Jianghua | Zhang, Panwei | Li, Kun | Yu, Liqin
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been demonstrated to be transferred from parental animals to their offspring. However, whether parental exposure to environmental concentrations of TDCIPP show neurodevelopmental toxicity in the F1 generation and the possible underlying mechanism remain unclear. Therefore, in this study, zebrafish embryos were exposed to environmental concentrations of TDCIPP (3, 30 and 300 ng L⁻¹) for 120 days. The effects of exposure on motor behaviors, neurotransmitter levels, DNA methylation, and gene expression of F1 larvae were investigated. Parental exposure left TDCIPP residues in F1 eggs as well as reduced body length of F1 larvae. Moreover, parental exposure significantly reduced swimming activity in F1 5 dpf larvae, although it did not significantly alter serotonin, dopamine, 3,4-dihydroxyphenylacetic acid, γ-aminobutyrate, and acetylcholine levels. Genes encoding DNA methylation transferases (dnmt3aa and dnmt1) were downregulated in F1 larvae. Reduced representation bisulfite sequencing analysis revealed 446 differentially methylated regions and enriched neuronal cell body Gene Ontology term in F1 generation. Correlation analysis between the expression of genes related to neural cell body and swimming speed indicated that solute carrier family 1 member 2b (slc1a2b) downregulation might be responsible for the inhibition of motor behaviors. Furthermore, bisulfite amplicon sequencing analysis confirmed hypermethylation of the promoter region of slc1a2b in F1 larvae following parental exposure to 300 ng L⁻¹ TDCIPP, which might have led to significant downregulation of gene expression and, in turn, influenced the motor behaviors. These results indicate that parental exposure to environmental concentrations of TDCIPP alters DNA methylation, downregulates gene expressions and, thus inducing developmental neurotoxicity, in F1 larvae.
Show more [+] Less [-]Toxicity of gabapentin-lactam on the early developmental stage of zebrafish (Danio rerio)
2021
He, Yide | Jia, Dantong | Du, Sen | Zhu, Rongwen | Zhou, Wei | Pan, Shunlong | Zhang, Yongjun
Gabapentin-lactam (GBP-L) is a transformation product (TP) of gabapentin (GBP), a widely used anti-epileptic pharmaceutical. Due to its high persistence, GBP-L has been frequently detected in the surface water. However, the effects of GBP-L on aquatic organisms have not been thoroughly investigated. In the present study, zebrafish (Danio rerio) embryos as a model organism were used to study the impacts of GBP-L in terms of embryos LC₅₀, spontaneous movement at 24 hpf (hours post fertilization), heartbeat rates at 48 hpf, and body length at 72 hpf, with the concentrations of GBP-L down to 0.01 μg/L, covering its environmental concentrations. Various biomarkers from nervous, antioxidant and immune systems of zebrafish larvae were analyzed, including acetylcholinesterase, acetylcholine, dopamine, gamma-aminobutyric acid, superoxide dismutase, catalase, glutathione S-transferase, C reactive protein, and lysozyme, to assess its toxicity on these systems. RT-qPCR was then used to further verify the results and explain the toxicological mechanism at the gene level. The results demonstrated that GBP-L is much more toxic than its parent compound, and could lead to adverse impacts on the aquatic organisms even at every low concentrations.
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