Research On Microrna Expression Profiles In Hippocampus Of Rats After Benzo[a] Pyrene Exposure

Objective: Built Benzo[a]pyrene(B[a]P)exposed rats hippocampal damage model,analysed the expression profile of microRNA(miRNA)in B[a]P-treated rat hippocampal tissue,screened differential expressed miRNAs,predicted the target genes of differential expressed mi RNAs,predicted the pathways involved in target genes,predicted the target genes of differentially expressed miRNA,to study the neurotoxicity mechanism of B[a]P.Methods: Eighteen primary male SD rats were adapted to feeding environment for 5 days,then randomly assigned to control group(n= 9)and B[a]P-treated group(n= 9,2.0 mg/kg KW).According to their body weight,they were continuously gavage for 7 weeks and the control group were given equal amount of corn oil.Detected learning and memory ability of rats after B[a]P-treated via Morris Water Maze(MWM).Observed ultrastructure of hippocampal neurons via electron microscope.Detected the miRNA expression profile of hippocampus via small RNA high-throughput sequencing technology.Differential expressed miRNAs were screened at more than 2 fold change(log2(fold change)> 1.0,P<0.05).Predicted the target genes of differential expressed miRNAs via three bioinformatics database(mi Randa,miRDB,and Target Scan 7.1).Pathway analysis of target genes via KEGG database and the PANTHER database in KOBAS platform.Results:(1)After 14 days of B[a]P exposure,body weight of B[a]P-treated rats were significantly lower than control group(P< 0.05).(2)MWM showed that compared with control group,escape latency of B[a]P-treated rats increased significantly(P< 0.05),the number of platform crossing and the time spent in target area decreased significantly(P< 0.05).(3)Electron microscopy results showed that swelled mitochondria,damaged myelin sheaths with stratification and collapse,and thickened postsynaptic density(PSD)(P= 0.042)in B[a]P-treated rats hippocampus.(4)The miRNA expression profiles of B[a]P-treated rats hippocampus were changed: 45 significant differential expressed miRNA were screened(log2(fold change)> 1.0,P< 0.05),of which 14 were up-regulated significantly,31 were down-regulated significantly.(5)Target gene prediction and functional analysis of differential expressed mi RNA revealed that 1 245,1445,and 4 444 target genes were predicted from miRanda,miRDB,and TargetScan 7.1 databases,respectively,and there were 1904 target genes shared by the three databases.The target genes of differential expressed miRNAs in B[a]P-treated rats have different functions,mainly related to synapses,signal transduction,mitochondrial energy metabolism,cellproliferation and apoptosis,cell cycle,nervous system diseases,and so on.Conclusion: B[a]P exposure can lead to the impairment of learning and memory ability in rats and change the ultrastructure of hippocampus.The possible neurotoxic mechanism was the change of miRNA expression profile,affectted the regulation of target genes by miRNAs,ultimately affect the synapses,signal transduction,mitochondrial energy metabolism,cell proliferation and apoptosis,cell cycle and other physiological processes.