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Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine. [ABSTRACT FROM AUTHOR]

Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine.

Gene by environment interactions (G × E) are thought to underlie neurodevelopmental disorder, etiology, neurodegenerative disorders, including the multiple forms of autism spectrum disorder. However, there is limited biological information, indicating an interaction between specific genes and environmental components. The present study focuses on a major component of airborne pollutants, polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene [B(a)P], which negatively impacts cognitive development in children who have been exposed in utero. In our study, prenatal exposure of Cprlox/lox timed-pregnant dams to B(a)P (0, 150, 300, and 600 μg/kg body weight via oral gavage) on embryonic day (E14–E17) consistent with our susceptibility-exposure paradigm was combined with the analysis of a replicated autism risk gene, the receptor tyrosine kinase, Met. The results demonstrate a dose-dependent increase in B(a)P metabolite generation in B(a)P-exposed Cprlox/lox offspring. Additionally, a sustained persistence of hydroxy metabolites during the onset of synapse formation was noted, corresponding to the peak of Met expression. Prenatal B(a)P exposure also downregulated Met RNA and protein levels and dysregulated normal temporal patterns of expression during synaptogenesis. Consistent with these data, transcriptional cell–based assays demonstrated that B(a)P exposure directly reduces human MET promoter activity. Furthermore, a functional readout of in utero B(a)P exposure showed a robust reduction in novel object discrimination in B(a)P-exposed Cprlox/lox offspring. These results confirm the notion that common pollutants, such as the PAH B(a)P, can have a direct negative impact on the regulated developmental expression of an autism risk gene with associated negative behavioral learning and memory outcomes. [ABSTRACT FROM AUTHOR]

Exposure to lead and other heavy metals is now considered a risk factor in fetal and early childhood developmental deficits, premature birth, low cranial circumference, lower IQ, learning disabilities, attention deficit disorders (ADD) or hyperactivity (ADHD), and reduced impulse control. Studies suggest that blood lead levels as low as 10 micrograms per deciliter can result in detectable physical, cognitive, and psychobehavioral deficits in children. According to recent CDC findings, the major sources of lead exposure include deteriorated paint in older housing, and dust and soil that are contaminated with lead from old paint and from past emissions of leaded gasoline. Further, the direct effects of poor diet on children's behavior combined with exposure to toxic metals increase the likelihood of attention deficit disorder (ADD), hyperactivity, and other learning deficits. Poor urban populations and minorities are at increased risk for these effects of neurotoxicity, because the problems of poverty and broken families often co-vary with inadequate diet, housing that contains lead paint and water systems that release lead, inadequate prenatal health care, high rates of bottle feeding, and exposure to industrial pollution. [ABSTRACT FROM AUTHOR]

In this study, zebrafish larvae are introduced as an in vivo platform to examine the neurotoxicity and developmental toxicity associated with continuous exposure to a concentration gradient of different sizes of SiO2 nanoparticles (15 nm and 50 nm diameter) to determine the dose effect and size effect of SiO2 nanoparticle (NP)-induced toxicity. Bovine serum albumin (BSA-V) is utilized as a stabilizing agent to prevent coagulation of the SiO2 nanoparticles. To the best of our knowledge, this study is the first to describe locomotor activity assays linking rest/wake behavioral profiles for the purpose of investigating the neurotoxicity of NPs. In addition, developmental toxicological endpoints including mortality, LC50 , malformation, and cartilaginous deformity are assessed. The results show a concentration-dependent increase in behavioral neurotoxicity, mortality, and malformation among larvae treated with the SiO2 nanoparticles of 15 nm and 50 nm. A comparison of the 15 nm and 50 nm NPs by K-means clustering analysis demonstrates that the 15 nm NPs have a greater neurotoxic effect than the 50 nm NPs, with the 50 nm NPs exhibiting greater developmental toxicity on the zebrafish larvae than the 15 nm NPs., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)