Chemical pollutants, such as pesticides, often leach into aquatic environments and impact non-target organisms. Marine invertebrates have complex life cycles with multiple life-history stages. Exposure to pesticides during one life-history stage potentially influences subsequent stages; a process known as a carry-over effect. Here, we investigated carry-over effects on the jellyfish Aurelia coerulea. We exposed polyps to individual and combined concentrations of atrazine (2.5 μg/L) and chlorpyrifos (0.04 μg/L) for four weeks, after which they were induced to strobilate. The resultant ephyrae were then redistributed and exposed to either the same conditions as their parent-polyps or to filtered seawater to track potential carry-over effects. The percentage of deformities, ephyrae size, pulsation and respiration rates, as well as the metabolic profile of the ephyrae, were measured. We detected a subtle carry-over effect in two metabolites, acetoacetate and glycerophosphocholine, which are precursors of the neurotransmitter acetylcholine, important for energy metabolism and osmoregulation of the ephyrae. Although these carry-over effects were not reflected in the other response variables in the short-term, a persistent reduction of these two metabolites could have negative physiological consequences on A. coerulea jellyfish in the long-term. Our results highlight the importance of considering more than one life-history stage in ecotoxicology, and measuring a range of variables with different sensitivities to detect sub-lethal effects caused by anthropogenic stressors. Furthermore, since we identified few effects when using pesticides concentrations corresponding to Australian water quality guidelines, we suggest that future studies consider concentrations detected in the environment, which are higher than the water quality guidelines, to obtain a more realistic scenario by possible risk from pesticide exposure.

Microcystin-LR (MCLR) has been reported to cause developmental neurotoxicity in zebrafish, but there are few studies on the mechanisms of MCLR-induced transgenerational effects of developmental neurotoxicity. In this study, zebrafish were exposed to 0, 1, 5, and 25 μg/L MCLR for 60 days. The F1 zebrafish embryos from the above-mentioned parents were collected and incubated in clean water for 120 h for hatching. After examining the parental zebrafish and F1 embryos, MCLR was detected in the gonad of adults and F1 embryos, indicating MCLR could potentially be transferred from parents to offspring. The larvae also showed a serious hypoactivity. The contents of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, gamma-aminobutyric acid (GABA) and acetylcholine (ACh) were further detected, but only the first three neurotransmitters showed significant reduction in the 5 and 25 μg/L MCLR parental exposure groups. In addition, the acetylcholinesterase (AChE) activity was remarkably decreased in MCLR parental exposure groups, while the expression levels of manf, bdnf, ache, htr1ab, htr1b, htr2a, htr1aa, htr5a, DAT, TH1 and TH2 genes coincided with the decreased content of neurotransmitters (dopamine, DOPAC and serotonin) and the activity of AChE. Neuronal development related genes, α1-tubulin, syn2a, mbp, gfap, elavl3, shha and gap43 were also measured, but gap43 was the gene only up-regulated. Our results demonstrated MCLR could be transferred to offspring, and subsequently induce developmental neurotoxicity in F1 zebrafish larvae by disturbing the neurotransmitter systems and neuronal development.

Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnα7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. ɑ1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons.

The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 μg/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, α1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, α1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.

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.

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.

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.

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.

Aging is an ultimate reality that everyone has to face. D-galactose (D-gal) has been used extensively to develop aging model. Trace elements such as selenium (Se) have been used as a potential antioxidant for neuro-protection. The present work aims to develop therapeutic agents such as Se for the treatment of aging-induced neurological ailments such as anxiety, depression, and memory impairment. For this purpose, mice were treated with D-gal at a dose of 300 mg/ml/kg and various doses of Se (0.175 and 0.35mg/ml/kg) for 28 days. Behavioral tests were monitored after treatment days. After the behavioral assessment, mice were decapitated and their brains were collected. Hippocampi were removed from the brain for biochemical, neurochemical, and histopathological analysis. The present findings of behavioral analysis showed that D-gal-induced anxiety- and depression-like symptoms were inhibited by both doses of Se. D-gal-induced memory alteration was also prevented by repeated doses of Se (0.175 and 0.35mg/ml/kg). Biochemical analysis showed that D-gal-induced increase of oxidative stress and inflammatory markers and decrease of antioxidant enzymes and total protein contents in the hippocampus were prevented by Se administration. An increase in the activity of acetylcholinesterase was also diminished by Se. The neurochemical assessment showed that D-gal-induced increased serotonin metabolism and decreased acetylcholine levels in the hippocampus were restored by repeated treatment of Se. Histopathological estimations also exhibited; normalization of D-gal induced neurodegenerative changes. It is concluded that D-gal-induced dysfunction in mice hippocampus caused anxiety, depression, memory impairment, oxidative stress, neuro-inflammation, and histological alterations that were mitigated by Se via its antioxidant potential, anti-inflammatory property, and modulating capability of serotonergic and cholinergic functions.

Hazard and risk associated with the use of radiotherapy play a crucial role in brain injury with interference via the neuroendocrine activity of the cancer survivors, and there is no effective preventive strategy. We conducted this study to assess the effect of citicoline in biosynthesis variants occurring in the cerebral cortex of rats in response to head γ-irradiation. Bio-analysis includes MDA, 8-OHdG, and NO as oxidation indicators; total antioxidant activity; the inflammatory factors TNF-α, IL-1β, and amyloid-β 42 levels; the caspase-3 cell death marker; IGF-I; serum hormones including GH, ACTH, FSH, and LH; and the neurotransmitters acetylcholine, dopamine, and serotonin. We exposed animals to 10 Gy head gamma irradiation followed by citicoline treatment and sustained for 30 days. The animals were sacrificed at the 3rd and 30th day post-irradiation. Citicoline mechanism has been linked to potent radical reduced ability counteracting the oxidative stress–mediated inflammation and apoptosis. Citicoline treatment has normalized the altering recorded in serum hormones associated with a significant modulation in the levels of IGF-1/PI3K/AKT factors. Such improvements have been concomitant with regulated neurotransmitter levels. We could conclude that citicoline may safely be supplemented to avoid both short- and long-term damages to the neuroendocrine disturbances, oxidative stress, inflammation, and apoptosis induced by head irradiation.