Biological Trace Element Research

, Volume 189, Issue 2, pp 463–477 | Cite as

Differential Expression of miRNAs in the Hippocampi of Offspring Rats Exposed to Fluorine Combined with Aluminum during the Embryonic Stage and into Adulthood

  • Qi-Di Ge
  • Chun XieEmail author
  • Hua Zhang
  • Ying Tan
  • Chang-Wu Wan
  • Wen-Juan Wang
  • Ting-Xu Jin


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 AlCl3 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.


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.


Fluorine Aluminum Hippocampus Learning and memory MicroRNAs 



High-throughput sequencing were conducted by RiboBio Biotechnology, Guangzhou, China.

Funding Information

This work was supported by the National Natural Science Foundation of China (Grant No. 81560519) and the Guizhou Science and Technology Support Plan (Grant No. [2018]2753).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Occupational Health and Environmental Hygiene, School of Public HealthGuizhou Medical UniversityGuiyangChina
  2. 2.Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of EducationGuizhou Medical UniversityGuiyangChina
  3. 3.Department of Forensic Pathology, School of Forensic MedicineGuizhou Medical UniversityGuiyangChina

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