The Effect Of Pregnancy/Lactation Arsenic Exposure On Sema3a Expression In The Brain Tissue Of Offspring Mice

Background Environmental arsenic pollution has become an increasinglyprominent health problems, exposed to chronic arsenic and its compounds can causearsenic accumulation in the body, causing multi-system injury. A large number ofepidemiological and animal experiments show that chronic arsenic exposure hasneurotoxic effects, especially in the perinatal and developmental stages are moresensitive to the neurotoxicity of arsenic in humans and animals. Therefore, low-levelarsenic exposure, pregnancy/lactation-induced nervous system damage and itsmechanism, has become a hot topic of concern in today’s scholars from variouscountries.Learning and memory is one of the important functions of the nervous system Atpresent, there are many scholars that is closely related to synaptic plasticity and learningand memory, synaptic plasticity is divided into functional plasticity and structuralplasticity, the plasticity of synaptic structure must be achieved through the axonterminal growth cone. Research has shown that arsenic exposure in the development canaffect the growth of axons, while sema3a as the axon guidance factors play an importantregulatory role in the normal growth of the axon. Thus, pregnancy/lactation arsenicexposure affect Sema3a expression, which is concerned to us.Objective Observation of arsenic on the axon guidance factors sema3a expressionin the developmental stages of brain tissue of pups in genetic and protein levels, in orderto clarify the brain development of arsenic exposure to the toxic effects of learning andmemory mechanisms of target gene basis.Methods Kunming pregnant mice were randomly divided into four groups: thecontrol group、1ppm As2O3、2ppm As2O3、4ppm As2O3(n=6).The female ratscontinue to arsenic exposure during pregnancy and lactating from0days of gestation,stopping to breastfeed3weeks postpartum. Partial off neck21days after the birth of the pups were sacrificed, specimens of brain tissue were placed in-80oC freezer curing.Behavioral test analyze the learning and memory of arsenic exposure during pregnancyto21days postpartum mice. GeneChip screen offspring brain development gene,Real-time PCR detect axon guidance factors Sema3a different expression in mRNAlevels, further confirmed by Western blot at the protein level. The distribution ofGAP43in growth cone membrane expression was detected by immunohistochemicalmethods.Using SPSS11.5statistical software, ANOVA analysis, comparison ofsignificant difference between the arsenic group and control group with LSD analysis,statistically significant differences (P<0.05) between the two groups.Result Step down test results show that with the increase of exposure dose, thelatency of jumping from the platform reduced and the occurrence of errors increased.Genechip screen that expression of the gene related brain development includingsema3a、RhoA、Rock1、Rock2、cRMPs was significantly upregulated. Real-timeRT-PCR、Western blot analysis showed that21days of birth of offspring cerebellumtissue Sema3a expression at the gene and protein levels in the arsenic exposure groupswere significantly increased and showed a dose-responsive relationship(p<0.05);Immunohisto-chemical results showed that compared with control group, arsenicexposed group GAP43expression significantly downregulated and showed a cleardose-response relationship.Conclude Pregnancy/lactation arsenic exposure affect offspring learning andmemory function, offspring brain tissue Sema3a expression was upregulated at geneand protein levels, GAP43protein expression was donwregulated in the growth conemembrane. Sema3a is likely to be target genes of arsenic neurotoxicity, and closelyrelated to arsenic affecting offspring learning and memory functions.