Xylene and its derivatives are known to be neurotoxic to the central nervous system of animals. Our previous work has shown that para-xylene (PX) can cause an increase in apoptotic cells and abnormal avoidance behavior in Xenopus laevis. However, the mechanism underlying the impact of PX on neuronal structural and functional plasticity is less clear. Here, we examined the effects of PX on neuronal development and plasticity in the developing optic tectum. We found that HuC/D-positive neurons were more vulnerable than SOX2-positive progenitor cells or BLBP-positive radial glial cells after exposure to PX at 1 mM for 48 h. The further measurement of postsynaptic receptors and synaptic vesicle proteins showed that the expression levels of GluA1 and GluA2, but not Rab3a and SNAP25, were significantly decreased in the tectal brain. In vivo time-lapse images and electrophysiological recordings showed that PX exposure resulted in significant deficits in neuronal structure, particularly in the total dendritic branch length (TDBL), and visual stimulation-induced excitatory compound synaptic currents (eCSCs) without altering neurotransmitter release probability. Strikingly, coexposure to d-glucuronolactone (GA) and PX rescued the structural and functional deficits caused by PX exposure alone. Furthermore, we found that visual experience-induced structural, functional and behavioral plasticity was blocked by PX exposure, which was also rescued by the simultaneous administration of GA and PX . Thus, our findings indicate that PX is neurotoxic to brain development and plasticity and that GA may be considered a promising candidate to treat PX-induced defects in neural circuits.

中文翻译：

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d-葡萄糖醛酸内酯可减弱对二甲苯诱导的非洲爪蟾体内神经元发育和可塑性的缺陷。

已知二甲苯及其衍生物对动物的中枢神经系统具有神经毒性。我们以前的工作表明对二甲苯（PX）可以导致非洲爪蟾的凋亡细胞增加和异常回避行为。但是，PX对神经元结构和功能可塑性的影响的机制尚不清楚。在这里，我们检查了PX对视神经发育中的神经元发育和可塑性的影响。我们发现，HuC / D阳性神经元比SOX2阳性祖细胞或BLBP阳性放射状神经胶质细胞更易受1 mM的PX照射48小时。对突触后受体和突触小泡蛋白的进一步测量显示，在顶盖脑中，GluA1和GluA2的表达水平显着降低，而Rab3a和SNAP25则没有显着降低。体内延时图像和电生理记录表明，PX暴露会导致神经元结构显着缺陷，尤其是总树突分支长度（TDBL）和视觉刺激诱导的兴奋性复合突触电流（eCSCs），而不会改变神经递质释放的可能性。令人惊讶的是，共同暴露于d-葡萄糖醛酸内酯（GA）和PX可以挽救仅由PX暴露引起的结构和功能缺陷。此外，我们发现视觉体验诱导的结构，功能和行为可塑性被PX暴露所阻断，而GA和PX的同时施用也挽救了这种风险。因此，我们的发现表明PX对大脑发育和可塑性具有神经毒性，GA可能被认为是治疗PX引起的神经回路缺损的有前途的候选药物。