Developmental Exposure To Nonylphenol Induced Myelin Injury Through The Activation Of TGF? R?-Smad2/3 Cascade In Cerebellum

Objective: Nonylphenol(NP)is a typical persistent organic pollutants(POPs),which leads to serious environmental pollution.The central nervous system(CNS)is very sensitive to POPs during development.Increasing evidence suggests that NP exposure during pregnancy and lactation can damage CNS in offspring.Myelin is abundant in the cerebellum,it is the basic and necessary structure of CNS,and the impact of NP exposure during pregnancy and lactation on the myelin sheath of offspring needs to be developed urgently.Therefore,we established a model of NP exposure during pregnancy and lactation to study the effects of NP on cerebellum-dependent motor function and myelin sheath development in offspring;to study the increase in oligodendrocytes(myelin forming cells);Based on the above studies,we investigated the relationship between changes in the TGF? RII-Smad2 / 3 signaling pathway(a signaling pathway that regulates oligodendrocyte proliferation)and NP exposure caused by myelin damage in the offspring.Methods: Male SD rats were randomly divided into control group,NP treatment group and positive control group.From the 0th day of pregnancy(GD0)to the 21 st day after birth of the offspring(PND21),the NP-exposed group was administered different doses of NP(corn oil as solvent,10,50 mg / kg / day)by gavage.Corn oil was given intragastrically every day.The positive control group was given intraperitoneal injection of valproic acid(VPA)at GD12.5 in addition to intragastrically given corn oil.At PND40,perform cerebellum-dependent behavioral experiments on the offspring to observe behavioral changes;perform immunofluorescence experiments to detect changes in cerebellar myelin development morphology;Take PND14 offspring cerebellar tissue to perform immunoblot experiments to detect the expression of TGF? RII-Smad2 / 3 and related proteins in myelin development signal pathway;perform immunofluorescence assay to detect oligodendrocyte precursor cells(OPCs)Change in value-added status.Results: Cerebellar-related behavioral changes in offspring exposed to NP during pregnancy and changes in myelin density at PND40.At PND14,NP exposure during pregnancy and lactation activates TGF?RII and p-Smad2 / 3 in the cerebellum of the pups,and changes the expression of SP1,p21,c-Myc proteins in the pups' cerebellum,and reduces the number of OPCs in the pups' cerebellum value-added state.Conclusion: 1.Exposure to NP during gestation causes changes in the cerebellum-related behaviors in the offspring and reduces the density of the myelin sheath in the offspring cerebellum.2.NP exposure activates the TGF? RII-Smad2 / 3 signaling pathway in the cerebellum,and causes increased expression of SP1 and p21,and then inhibits the expression of c-Myc,which causes a decrease in the proliferation of oligodendrocyte precursor cells.3.The decrease of cerebellum myelin density caused by NP exposure may be due to the decrease in the increase of cerebellar OPCs,which may lead to the reduction of myelin formation.