Study On The Neurotoxic Effect Of SCCPs On Zebrafish

Short chain chlorinated parafins(SCCPs)are a class of synthetic chlorinated derivatives of straight-chain n-alkanes with complex composition,which are widely used in industry due to their excellent chemical properties.China is the largest producer and user of SCCPs all over the world,which also leads to the exposure situation of SCCPs in China is not optimistic that SCCPs are widely detected in environmental media and aquatic organisms.In addition,SCCPs are also highly toxic,persistent,bioaccumulative,and long-distance migratory,and because of these characteristics,SCCPs are classified as persistent organic pollutants(POPs)by the Stockholm Convention in 2017.Previous studies have shown that the toxic effects of SCCPs are mainly endocrine disrupting effects,metabolic disrupting effects,teratogenic,carcinogenic,and mutagenic “three-induced” effects etc.However,there is a lack of research on the neurotoxicity of SCCPs.Therefore,we use the model organism zebrafish as the research object to study the neurotoxicity effect of SCCPs on zebrafish,and to clarify the toxicity mechanism at the molecular level.It is of great significance for the environmental management and risk control of SCCPs in China.The main work of this study is as follows:(1)After fertilization 4 hpf,zebrafish embryos were exposed to 0 μg/L,25 μg/L,50 μg/L(environmental dose concentration),100 μg/L SCCPs to different developmental nodes(24 hpf and 120 hpf)to study the neurobehavioral effects of SCCPs exposure on zebrafish larvae.And the neurodevelopmental toxicity of SCCPs was studied by analyzing the expression levels of neurodevelopmental genes in zebrafish larvae after exposed to SCCPs to 120 hpf.Our study found that the spontaneous movement ability of zebrafish larvaes decreased after exposure to SCCPs from 4 hpf after fertilization to 24 hpf,and the free-swimming ability decreased significantly under light and dark stimulation after exposure to 120 hpf.The expression levels of neurodevelopmental related genes were affected,indicating that SCCPs exposure caused neurodevelopmental toxicity and neurobehavioral toxicity to zebrafish larvae.(2)5-month-old adult zebrafish were exposed to 0 μg/L,50 μg/L(environmental dose concentration),150 μg/L,250 μg/L SCCPs for 21 days.The neurotoxic effects and mechanisms of SCCPs on zebrafish were determined by free swimming behavior analysis,brain tissue pathological section,brain tissue transmission electron microscope observation,blood-brain barrier-related genes and protein expression levels,neurotoxicity-related and apoptosis genes expression levels.The conclusions were as follows: after 21 days of SCCPs exposure,the exercise capacity and activity of zebrafish decreased significantly.Also,the content and activity of acetylcholinesterase(ACh E)in brain tissue decreased significantly,which indicated that SCCPs exposure disturbed the cholinergic system by reducing the content and activity of ACh E in brain tissue,and caused the decrease of exercise capacity and activity of zebrafish.SCCPs exposure can damage the blood-brain barrier by destroying the tight junction structure,and can also lead to brain tissue necrosis.SCCPs exposure significantly down-regulated the expression of bdnf gene and up-regulated the expression of nse2,s-100 b,bax,caspase3,caspase8 and caspase9 genes,resulting in neurotoxicity on zebrafish.In summary,this study used the model organism zebrafish to study the neurotoxic effects of SCCPs.And finally,this research found that SCCPs reduced the locomotor ability of larvae and adult fish,destroyed the blood-brain barrier,affected the expression of functional genes in the nervous system,and activated the apoptotic pathway,which preliminarily revealed the neurotoxic effects and mechanisms of SCCPs.