Diazepam and Its Disinfection Byproduct Promote the Early Development of Nervous System in Zebrafish Embryos

The widely used diazepam, as central nervous system inhibitor, has found to be ubiquitous in surface water and drinking water. Moreover, a series of byproducts such as 2-methylamino-5-chlorobenzophenone (MACB) were generated after the chlorine disinfection process. However, little information is available about the neurobiological effects of these emerging chemicals at low doses, especially on infants and children. Here, we exposed zebrafish (Danio rerio) embryos to diazepam and MACB at 0.05, 0.5, and 5 nM, which were equivalent to environmental levels. Both diazepam and MACB increased the somite number and promoted nervous development of transgenic zebrafish [Tg (elavl3: EGFP) larvae] at 72 hours postfertilization ( hpf). Both diazepam and MACB also disrupted the homeostasis of adenosine monophosphate, valine, methionine, and fumaric acid in zebrafish embryos at 12 hpf. Additionally, the locomotor behavior activity of zebrafish was significantly enhanced after 120-hour sustained exposure to diazepam or MACB. Moreover, the mRNA expression levels of oct4, sox2, and nanog, modulating the pluripotency and self-renewal, were upregulated by diazepam and MACB in zebrafish embryo. Altogether, diazepam and MACB stimulate developmental neurogenesis and may induce neuronal excitotoxicity at quite low doses. These results indicated that the chronic exposure to psychoactive drugs may pose a potential risk to the development of the nervous system in infancy.

TMS: neurodevelopment and perinatal insults

Neural substrate for changes in neuromotor skills of typically developing children involves the complex and organized maturation of underlying brain structures. This article gives an overview of the changes that occur in motor function, as children get older and those aspects of central nervous development which may form the neural substrates of motor function development. It describes those TMS evoked parameters, related to the motor system, that have been studied in both typically developing children and in those who have suffered perinatal insults to the central nervous system. TMS has its limitations and is especially useful when used in combination with other neurophysiological modalities. The focus for future studies should be on correlating TMS evoked parameters with behavioural measures in typically developing children and explanation of the neural substrates of the motor abnormalities in children with perinatal insults and developmental disabilities.