| The serotonergic nervous system is the first nervous system detected during earlyembryogenesis in the sea urchin, and regulates morphological genesis and swimmingbehavior in the sea urchin. Organophosphate pesticides can interfere with theserotonergic nervous system and potentially lead to malformations and behavioralabnormalities. However, the underlying mechanisms behind how organophosphatepesticides affect this system are still not clear, and identifying these processes may beessential to understanding developmental neurotoxicity induced by organophosphatepesticides via noncholinergic pathways. Serotonin neurotransmitter is basallynecessary for the growth and projection of serotonergic neurons, and the formation ofthe serotonergic receptor cell network (SRCN). In addition to serotoninneurotransmitter itself, HpNetrin and its receptors functions as a serotonergic axonguidance cue regulating the genesis of serotonergic neuron and directional extensionof the serotonergic axons during early embryogenesis in the sea urchin. Therefore, theneurotoxic effects of organophosphate pesticides on the serotonergic nervous systemmay be related to a disruption of serotonin metabolism and expression of Netrin andits receptors.Fertilized embryos were incubated with40%MCP pesticide at nominalconcentrations of0.01,0.10and1.00mg/L based on median lethal concentration(LC50) during different developmental stages, and the effects on tryptophanhydroxylase of Hemicentrotus pulcherrimus (HpTPH), serotonin reuptake transporter(SERT), monoamine oxidase (MAO) and concentration of serotonin, and HpNetrinand its receptors were investigated. The time intervals were chosen according todevelopmental progression of the serotonergic nervous system: the12-hour postfertilization (12-hpf) early blastulae stage,15-hpf swimming blastulae stage,18-hpf early gastrulae stage,24-hpf late gastrulae stage,30-hpf early prism stage,36-hpfprism stage, and48-hpf two-arm pluteus stage. The present study sought to evaluatethe mechanism for how MCP pesticide disrupts the serotonergic nervous systemduring early development in the sea urchin, Hemicentrotus pulcherrimus, and toexplain the underlining mechanism of neurotoxic of organophosphate pesticides.These results indicated that:(1) There are some kinds of feedback regulation mechism maintaining the levels ofserotonin during early development in the sea urchin. Concentration of serotonin changed a littleafter exposed to the MCP pesticide, but activity of serotonin metabolize was affected which mightbe one of the major concern of MCP pesticide on serotonin metabolize. While serotonin should besmetabolized at low levels during normal development, HpTPH and SERTmRNA expression wasinduced by MCP, leading to an unnecessary increase in serotonin metaboliz. Conversely, whenHpTPH and SERT should be expressed at high baseline levels to satisfy the development of theserotonergic nervous system, its transcription was impaired, resulting in a shortage of serotoninmetaboliz. It can be concluded that this metabolic disturbance is one of the major mechanisms bywhich organophosphate pesticides affect the serotonergic nervous system and potentiallycontribute to various developmental abnormalities.(2) Expression of HpNetrin and its receptor neogenin was perturbed by MCPpesticide during early development in H. pulcherrimus. Before the development of theserotonergic nervous system, expression of HpNetrin and neogenin was elevated by0.01mg/L and0.10mg/L MCP pesticide and was decreased by1.00mg/L MCP pesticide,potentially leading to the disorder of serotonergic neuron genesis and interfere withdevelopment of serotonergic nervous system. While generation of serotonergic nervous systembegins, expression of HpNetrin and neogenin was elevated by MCP pesticide at all threeset concentrations. The neurotoxic effects of MCP pesticide on HpNetrin andneogenin expression would interfere with extension of the serotonergic axons.In present study, it’s clear that metabolic disturbance of serotonin neurotransmitter anddisorder of HpNetrin and its receptor expression would be potential mechanism for how MCPpesticide disrupts the serotonergic nervous system during early development in the seaurchin. |
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