| Since the human society entered the industrialization era,the mining and chemical industry has developed vigorously,which has led to the deterioration of metal pollution in water and soil environment.Most of the metal contaminants are difficult to be degraded by microorganisms,and gradually accumulate in the food chain.Subsequently,the enriched metals enter the human body,posing a serious health threat.Antimony is a silvery metal,it exists mainly as Sb(III)and Sb(V)in environmental.Existing studies have shown that almost all antimony and its compounds are toxic and have the ability to induce diseases of respiratory system,circulatory system and endocrine system,which have revealed the related cellular or molecular mechanisms.However,people have known little about the neurotoxic effects and underlying mechanism of antimony.In this study,we investigated the effects of antimony on the nervous system of zebrafish from phenotypic and behavioral levels,organs,tissues,cells and molecules..The results indicate that antimony is neurotoxic to zebrafish.The main results of this research are as follows: 1)After exposure,zebrafish embryos showed abnormal phenotypes such as shortened body length,morphological malformation,and weakened heart rate,which became more serious with the increase of concentration.2)Behavioral experiments indicated that the embryonic spontaneous movement was suppressed after exposure in a concentration-dependent manner during 19-27 hpf;the tail-contact level decreased at 27 hpf and 36 hpf;the total move distance and average speed of larvae dramatically decreased,and the trajectory is disorderly at 120 hpf.3)Using Tg(flk:EGFP)and Tg(gfap:GFP)zebrafish combined with laser confocal imaging,we found that antimony can cause cerebral vascular decrease and deformity in zebrafish.The expression intensity and distribution of Gfap in the brain also changed significantly.4)In order to explore the neurotoxic mechanism of antimony,we further detected the level of ROS,the activity of neurotransmitters,the expression of marker genes and other indicators in zebrafish.We found that with the increase of antimony concentration,the level of ROS gradually increased,and the activity or content of antioxidant enzymes decreased.Antimony causes a decrease in ACh E levels,along with a decreased expression of neurofunctional markers such as gfap,nestin,mbp,and shha in zebrafish embryos.In addition,the neurotoxicity of antimony on adult zebrafish has also been preliminarily investigated.We observed darker color,slower movement and poorer coordination of the treated fish.The T-maze experiment showed that the learning and memory abilities of the fish were decreased.According to tissue section,HE staining,LFB myelin staining,Congo red staining and Nissl staining,the results showed that antimony had a significant inhibitory effect on the neuron development of adult zebrafish.In conclusion,our study shows that antimony ions in the soil and water environment can damage the structure and function of the nervous system of zebrfish by increasing the level of oxidative stress in vivo,inhibiting the function of neurotransmitters and interfering with the expression of some neuro-related genes,and thus leading to the abnormal phenotypes and behaviors in organisms.These results not only promote our understanding of the neurotoxicity of antimony,but also suggest that the accumulation and transmission of antimony in the environment may have potential adverse effects on the human nervous system. |
