The Toxicity Assessment Of Fluoride In Mice Brain Through Transcriptomices And Protoemics

Fluoride is widespread in the environment of our daily life.Although the primary study has indicated its beneficial effects in dental caries,the additional investigation revealed fluoride could easily across the blood-brain-barrier and the placenta.The accumulation of fluoride in human body could cause the damage of neuron apoptosis,neuroinflammation and intellectual disabilities during fetus and newborns development.Thus,it is necessary to conduct the study on two-generational toxicity assessment of fluoride in mice brain and its detailed mechanisms.In our study,the continuous filial generation mice were given NaF in their drinking water(parents for 60 days and offspring for 30 days)with different concentrations(0 mg/L,10 mg/L and 50 mg/L,respectively).Then we collected brain tissue of all groups and extracted the total RNA and proteome for transcriptomic and proteomic study.The "omics"data was combined and compared between different dosage of NaF treatment and parent-offspring groups.In this way,we successfully outlined gene response pattern between those groups,and we further attempted to uncover the molecular mechanism and core regulatory gene network and related proteins.The result of our study indicated that:the influence of fluoride induced brain damage was not simply dose-effect.In parental groups,fluoride mainly affected neuron activities and nerve system,in offspring groups,fluoride could dramatically elevate immunity related processes and suppress nerve system relatively weaker.There might be a repair mechanism during offspring neurodevelopment upon fluoride toxicity.Through combined network analysis,the core regulatory factors like:Notch1,Kit,Smad6,Lef1 and Tal1,could regulate neurodevelopment and several important cellular signaling pathways.In conclusion,our study has explored the chronic fluoride exposure induced neuronal damage and neurodevelopmental alteration in parent-offspring mice brain,we further promoted novel regulatory nodes and a signaling pathway network.It provided fundamental evidence for conducting fluoride induced neuronal damage mechanism and protective processes.