Low-dose chronic lead (Pb) exposure interferes with the development of the nervous system, which may lead to learning disabilities, behavioral abnormalities, and mental retardation. Neurexins (Nrxns) are synaptic cell-adhesion molecules associated with neurological disorders. We hypothesized that Pb can affect the expression of nrxns during synapse formation and alter the phenotype behavior. Here, apoptosis, nrxns mRNA expression, and alterations of locomotion were examined after exposure to Pb in zebrafish embryos/larvae. To confirm the function of nrxn2a, rescue experiments were performed using β-nrxn2a mRNA microinjection. Pb exposure increased apoptosis and altered locomotor behavior in zebrafish larvae. Quantitative PCR showed that among several synaptic adhesion molecules, only nrxn2a were affected by Pb exposure. Moreover, exposure to Pb at 10 μmol/L upregulated mRNA expression of nrxn1a and nrxn3a at 24 h post fertilization (hpf) and downregulated expression at 48 hpf, whereas the expression remained unchanged at 72 hpf. Only the two isoforms of nrxn2a were downregulated by Pb at 10 μmol/L at all three time points. Rescue experiments showed that β-nrxn2a mRNA injection recovered the decreased locomotor activity and the increased apoptosis induced by Pb. In addition, overexpression of β-nrxn2a mRNA upregulated α-nrxn2a. These data indicated that Pb inhibited the expression of nrxn2a genes, which play a critical role in neural development, and further altered the behavior of zebrafish embryos/larvae.

低剂量慢性铅（Pb）暴露会干扰神经系统的发育，这可能导致学习障碍，行为异常和智力低下。神经毒素（Nrxns）是与神经系统疾病相关的突触细胞粘附分子。我们假设铅可以影响突触形成过程中nrxns的表达并改变表型行为。在这里，在斑马鱼胚胎/幼虫中暴露于Pb后，检查细胞凋亡，nrxns mRNA表达和运动变化。为了证实nrxn2a的功能，使用β - nrxn2a进行了抢救实验。mRNA微量注射。铅暴露增加了斑马鱼幼虫的凋亡并改变了其运动行为。定量PCR显示，在几个突触粘附分子中，只有nrxn2a受铅暴露的影响。而且，暴露于10μmol/ L的Pb会在受精后24 h（hpf）上调nrxn1a和nrxn3a的mRNA表达，并在48 hpf下调其表达，而在72 hpf下则保持不变。在所有三个时间点，只有10nmol / L的Pb下调了nrxn2a的两个同工型。救援实验表明，注射β-nrxn2amRNA可以恢复铅引起的运动活性降低和凋亡增加。另外，β过表达- nrxn2a表达上调α - nrxn2a。这些数据表明，Pb抑制了nrxn2a基因的表达，该基因在神经发育中起关键作用，并进一步改变了斑马鱼胚胎/幼虫的行为。