PMID- 30033483 OWN - NLM STAT- MEDLINE DCOM- 20190802 LR - 20200930 IS - 1559-0720 (Electronic) IS - 0163-4984 (Linking) VI - 189 IP - 2 DP - 2019 Jun TI - Differential Expression of miRNAs in the Hippocampi of Offspring Rats Exposed to Fluorine Combined with Aluminum during the Embryonic Stage and into Adulthood. PG - 463-477 LID - 10.1007/s12011-018-1445-4 [doi] AB - A previous study from our team found that continuous exposure to fluorine combined with aluminum (FA) impaired the neurobehavioral reflexes, spatial learning, and memory of offspring rats. To date, the specific mechanisms for these changes are unclear. Here, high-throughput sequencing was utilized to analyze the microRNA (miRNA) profile of the hippocampi in the offspring of rats exposed to FA during the embryonic stage and into adulthood through tap water supplemented with NaF and AlCl(3) at concentrations of (0, 0); (60, 600); (120, 600); and (240, 600) mg/L, respectively. qRT-PCR was performed to validate the reliability of the sequence data. Twenty differentially expressed miRNAs were selected for further analysis using bioinformatics tools. Several genes related to neuromodulation were found to be regulated by miR-10a-5p, miR-34b-5p, and miR-182, which might be harmful to normal nerve function. The protein levels of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in hippocampus were markedly downregulated. These data suggest that miR-10a-5p, miR-34b-5p, and miR-182 and BDNF-TrkB signaling pathway are involved in mechanisms of hippocampal damage in the offspring of rats exposed to FA. HIGHLIGHTS: * Multiple miRNAs were significantly differentially expressed in offspring rat hippocampus after fluorine combined with aluminum (FA) exposure. * Twenty differentially expressed miRNAs might mediate FA-induced developmental neurotoxicity. * MiR-10a-5p, miR-34b-5p, and miR-182 were closely related to neurotoxic signaling of FA. * The BDNF-TrkB learning and memory-associated pathway was downregulated in the hippocampus after FA exposure. FAU - Ge, Qi-Di AU - Ge QD AD - Department of Occupational Health and Environmental Hygiene, School of Public Health, Guizhou Medical University, University Town, Guian new district, Guiyang, 550025, Guizhou, China. AD - Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, Guizhou, China. FAU - Xie, Chun AU - Xie C AUID- ORCID: 0000-0002-4723-9890 AD - Department of Occupational Health and Environmental Hygiene, School of Public Health, Guizhou Medical University, University Town, Guian new district, Guiyang, 550025, Guizhou, China. xiechun36@163.com. AD - Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, Guizhou, China. xiechun36@163.com. FAU - Zhang, Hua AU - Zhang H AD - Department of Occupational Health and Environmental Hygiene, School of Public Health, Guizhou Medical University, University Town, Guian new district, Guiyang, 550025, Guizhou, China. AD - Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, Guizhou, China. FAU - Tan, Ying AU - Tan Y AD - Department of Occupational Health and Environmental Hygiene, School of Public Health, Guizhou Medical University, University Town, Guian new district, Guiyang, 550025, Guizhou, China. AD - Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, Guizhou, China. FAU - Wan, Chang-Wu AU - Wan CW AD - Department of Forensic Pathology, School of Forensic Medicine, Guizhou Medical University, Guiyang, 550004, Guizhou, China. FAU - Wang, Wen-Juan AU - Wang WJ AD - Department of Occupational Health and Environmental Hygiene, School of Public Health, Guizhou Medical University, University Town, Guian new district, Guiyang, 550025, Guizhou, China. AD - Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, Guizhou, China. FAU - Jin, Ting-Xu AU - Jin TX AD - Department of Occupational Health and Environmental Hygiene, School of Public Health, Guizhou Medical University, University Town, Guian new district, Guiyang, 550025, Guizhou, China. AD - Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, Guizhou, China. LA - eng GR - [2018]2753/the Guizhou Science and Technology Support Plan/ GR - 81560519/the National Natural Science Foundation of China/ PT - Journal Article DEP - 20180722 PL - United States TA - Biol Trace Elem Res JT - Biological trace element research JID - 7911509 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN10 microRNA, rat) RN - 0 (MicroRNAs) RN - 284SYP0193 (Fluorine) RN - CPD4NFA903 (Aluminum) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) MH - Aluminum/*toxicity MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Female MH - Fluorine/*toxicity MH - Hippocampus/drug effects/*metabolism MH - Male MH - MicroRNAs/*metabolism MH - Rats MH - Receptor, trkB/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Spatial Learning/drug effects OTO - NOTNLM OT - Aluminum OT - Fluorine OT - Hippocampus OT - Learning and memory OT - MicroRNAs EDAT- 2018/07/24 06:00 MHDA- 2019/08/03 06:00 CRDT- 2018/07/24 06:00 PHST- 2018/02/27 00:00 [received] PHST- 2018/07/12 00:00 [accepted] PHST- 2018/07/24 06:00 [pubmed] PHST- 2019/08/03 06:00 [medline] PHST- 2018/07/24 06:00 [entrez] AID - 10.1007/s12011-018-1445-4 [pii] AID - 10.1007/s12011-018-1445-4 [doi] PST - ppublish SO - Biol Trace Elem Res. 2019 Jun;189(2):463-477. doi: 10.1007/s12011-018-1445-4. Epub 2018 Jul 22.