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.

Excessive exposure to cobalt (Co) is known to make adverse impact on the nervous system, but its detailed mechanisms of neurotoxicity have yet to be determined. In this study, C57BL/6 mice (0, 4, 8, 16 mg/kg CoCl₂, 30 days) and human neuroblastoma H4 cells (0, 100, 400, 600 μM CoCl₂) were used as in vivo and in vitro models. Our results revealed that CoCl₂ intraperitoneal injection caused significant impairments in learning and memory, as well as pathological damage in the nervous system. We further certificated the alteration of m⁶A methylation induced by CoCl₂ exposure. Our findings demonstrate for the first time, significant differences in the degree of m⁶A modification, the biological function of m⁶A-modified transcripts between cortex and H4 cell samples. Specifically, MeRIP-seq and RNA-seq elucidate that CoCl₂ exposure results in differentially m⁶A-modified and expressed genes, which were enriched in pathways involving synaptic transmission, and central nervous system (CNS) development. Mechanistic analyses revealed that CoCl₂ remarkably changed m⁶A modification level by affecting the expression of m⁶A methyltransferase and demethylase, and decreasing the activity of demethylase. We observed variation of m⁶A modification in neurodegenerative disease-associated genes upon CoCl₂ exposure and identified regulatory strategy between m⁶A and potential targets mRNA. Our novel findings provide novel insight into the functional roles of m⁶A modification in neurodegenerative damage caused by environmental neurotoxicants and identify Co-mediated specific RNA regulatory strategy for broadening the epigenetic regulatory mechanism of RNA induced by heavy metals.

Ambient ultrafine black carbon (uBC) can potentially cross blood-brain barrier, however, very little is currently known about the effects they may have on central nervous system. This study aimed to explore the roles of autophagy in Alzheimer-like pathogenic changes promoted by uBC in SH-SY5Y cells. We firstly found uBC could cause cytotoxicity and oxidative stress in SH-SY5Y cells. Additionally we found uBC initiated progressive development of Alzheimer's disease (AD) associated features, mainly including neuro-inflammation and phosphorylation of tau protein (p-Tau) accumulation. Meanwhile, autophagy process was activated by uBC probably through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. RNA interference and autophagosome-lysosome fusion inhibitor were applied to block autophagy process at different stages. Autophagy dysfunction at the initial membrane expansion stage could aggravate p-Tau accumulation and other Alzheimer-like changes in SH-SY5Y cells promoted by uBC. However, autophagy inhibition at the final stage could alleviate p-Tau accumulation caused by uBC. This suggested that inhibition of the infusion of autophagosome and lysosome could possibly activate ubiquitination degradation pathway to regulate p-Tau equilibrium in SH-SY5Y cells. Our findings further raise the concerns about the effects of uBC on the risk of AD and indicate potential roles of autophagy in early Alzheimer-like pathogenic changes caused by ambient uBC.

Triclosan (TCS) is an organic compound with a wide range of antibiotic activity and has been widely used in items ranging from hygiene products to cosmetics; however, recent studies suggest that it has several adverse effects. In particular, TCS can be passed to both fetus and infants, and while some evidence suggests in vitro neurotoxicity, there are currently few studies concerning the mechanisms of TCS-induced developmental neurotoxicity. Therefore, this study aimed to clarify the effect of TCS on neural development using zebrafish models, by analyzing the morphological changes, the alterations observed in fluorescence using HuC-GFP and Olig2-dsRED transgenic zebrafish models, and neurodevelopmental gene expression. TCS exposure decreased the body length, head size, and eye size in a concentration-dependent manner in zebrafish embryos. It increased apoptosis in the central nervous system (CNS) and particularly affected the structure of the CNS, resulting in decreased synaptic density and shortened axon length. In addition, it significantly up-regulated the expression of genes related to axon extension and synapse formation such as α1-Tubulin and Gap43, while decreasing Gfap and Mbp related to axon guidance, myelination and maintenance. Collectively, these changes indicate that exposure to TCS during neurodevelopment, especially during axonogenesis, is toxic. This is the first study to demonstrate the toxicity of TCS during neurogenesis, and suggests a possible mechanism underlying the neurotoxic effects of TCS in developing vertebrates.

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.

Risk assessments of the ecotoxicological effects insecticides impose on ectotherms have increasingly considered temperature. However, the changes toxicants induce in thermoregulatory behavioral traits may lead to a divergence of thermal selection and temperature-dependent changes of contaminant toxicity. This study demonstrated the interaction of behavioral thermoregulation and temperature-dependent toxicity of beta-cyfluthrin (BC) in the lizard Eremias argus. Based on the negative relationship between temperature and BC toxicity, seeking a warming environment was assumed to represent a self-rescue behavior (and vice versa). The results showed that BC-treated lizards (0–20 μg/g body weight (bw)) showed such self-rescue behavior, while lizards exposed to an extremely high BC dose (200 μg/g bw) sought a cooler environment. Biochemical assays showed that BC affected neurotransmitter systems, caused oxidative stress, and interfered with ion-transport in the central nervous system. Biomarkers of the cholinergic and glutamatergic system, ion-transport function, and oxidative stress were identified as potential biochemical variables related to thermoregulatory behavior. Apparently, seeking a warmer environment is a survival strategy with the aim to neutralize BC toxicity, while seeking a cooler environment aims to attenuate the harmful effects of metabolic and oxidative stress, and to decelerate internal BC diffusion. This phenomenon could be also explained by the concept of the “cooling trap”, i.e., a behavior where cooler temperatures are sought. This impairs survival after exposure to BC at it has a negative temperature coefficient, derived from a dysfunction of the central nervous system regarding thermoregulation caused by the high dosage of neurotoxicant and resulting temperature maladaptation. Implications of the interaction between thermoregulatory behavior and temperature-dependent toxicity are presented, which may aid further temperature-dependent risk assessments.

Toluene is a highly volatile organic solvent present in gasoline. Exposure mainly occurs by absorption via the pulmonary tract and easily reaches the central nervous system, which causes toxic effects. Toluene toxicity has been described but not well established. The present work aimed to evaluate the effects of airborne exposure to toluene, the in vivo model Caenorhabditis elegans was assessed to determine whether nematode could be used to evaluate the effects of exposure to toluene and the possible mechanisms of toxicity of the solvent. Worms at the first or fourth larval stages were exposed to toluene for 48 or 24 h, respectively, in a laboratory-developed vapor chamber at concentrations of 450, 850, 1250 and 1800 ppm. We observed increases in worm mortality and significant developmental delays that occurred in a concentration-dependent manner. An increased incidence of apoptotic events in treated germline cells was shown, which was consistent with observed reductions in reproductive capacity. In addition, toluene promoted significant behavioural changes affecting swimming movements and radial locomotion, which were associated with changes in the fluorescence intensity and morphology of GABAergic and cholinergic neurons. We conclude that toluene exposure was toxic to C. elegans, with effects produced by the induction of apoptosis and neuronal damage.

Bisphenol-A (BPA) is a type of Endocrine Disrupting Compound (EDC) that is being widely used in the production of polycarbonate and epoxy resins. Last few years, the human exposure to BPA has been extensively high due to continuous increment in Annual Growth Rate (AGR) of BPA global market. The presence and transportation of BPA in the environment could cause serious damage to the aquatic life and human health. In this paper, we have reviewed the literature on the exposure and toxicity mechanism of BPA and advanced analytical techniques for detection of BPA in environment and human beings. The study indicated that BPA can cause damaging effects on numerous tissues and organs, including reproductive system, metabolic dysfunction, respiratory system, immune system and central nervous system. On the basis of reported studies on animal indicates that the exposure of BPA can be the carcinogenic and responsible for causing a variety of cancers like ovarian cancer, uterine cancer, prostate cancer, testicular cancer and liver cancer. This review paper mainly focused on current progress in BPA removal technologies in last ten years (2012–2022). This paper presenting the comprehensive overview of individual removal technology including-adsorption, photocatalysis/photodegradation, ozonation/advance oxidation, photo-fenton, membrane/nanofilters, and biodegradation along with removal mechanism. The extensive literature study shows that each technology has its own removal mechanism and limitation in BPA treatment. In adsorption and membrane separation process, most of BPA has been treated by electrostatic interaction, hydrogen boning and π-π interations mechanism. Whereas in degradation mechanism, O* and OH* species has been played major role in BPA removal. Some factors could be altered the removal potential and efficiency of BPA removal. This review paper will provide a useful guide in providing directions for future investigation to address the problem of BPA-containing wastewater treatment.

The free radicals produced by cigarette smoking are responsible for tissue damage, heart and lung diseases, and carcinogenesis. The effect of tobacco on the central nervous system (CNS) has received increased attention nowadays in research. Therefore, to explore the molecular interaction of cigarette smoke carcinogens (CSC) 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK), and N′-nitrosonornicotine (NNN) with well-known targets of CNS-related disorders, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes, a cascade of the computational study was conducted including molecular docking and molecular dynamics simulations (MDS). The investigated results of NNAL+AChEcₒₘₚₗₑₓ, NNK+AChEcₒₘₚₗₑₓ, and NNK+BuChEcₒₘₚₗₑₓ based on intermolecular energies (∆G) were found to −8.57 kcal/mol, −8.21 kcal/mol, and −8.08 kcal/mol, respectively. MDS deviation and fluctuation plots of the NNAL and NNK interaction with AChE and BuChE have shown significant results. Further, Molecular Mechanics Poisson-Boltzmann Surface Area (MM‐PBSA) results shown the best total binding energy (ᴮⁱⁿᵈⁱⁿᵍ∆G) −87.381 (+/−13.119) kJ/mol during NNK interaction with AChE. Our study suggests that CSC is well capable of altering the normal biomolecular mechanism of CNS; thus, obtained data could be useful to design extensive wet laboratory experimentation to know the effects of CSC on human CNS.

Eleven piperazine-containing 1,3-diphenylprop-2-en-1-one derivatives (PC1-PC11) were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with a view toward developing new treatments for neurological disorders. Compounds PC10 and PC11 remarkably inhibited MAO-B with IC₅₀ values of 0.65 and 0.71 μM, respectively. Ten of the eleven compounds weakly inhibited AChE and BChE with > 50% of residual activities at 10 μM, although PC4 inhibited AChE by 56.6% (IC₅₀ = 8.77 μM). Compound PC3 effectively inhibited BACE-1 (IC₅₀ = 6.72 μM), and PC10 and PC11 moderately inhibited BACE-1 (IC₅₀ =14.9 and 15.3 μM, respectively). Reversibility and kinetic studies showed that PC10 and PC11 were reversible and competitive inhibitors of MAO-B with Kᵢ values of 0.63 ± 0.13 and 0.53 ± 0.068 μM, respectively. ADME predictions for lead compounds revealed that PC10 and PC11 have central nervous system (CNS) drug-likeness. Molecular docking simulations showed that fluorine atom and trifluoromethyl group on PC10 and PC11, respectively, interacted with the substrate cavity of the MAO-B active site. Our results suggested that PC10 and PC11 can be considered potential candidates for the treatment of neurological disorders such as Alzheimer’s disease and Parkinson’s disease.