Abstract
Perfluorooctanoic acid (PFOA) is a member of Per- and polyfluoroalkyl substances (PFASs), an industrial pollutant that has been produced for decades and widely used in various industries. Accumulation of this compound in the environment and body of organisms led to increased concerns about this compound. The toxic effects of PFOA on the nervous system are unknown yet. We aimed to assess the myelination and neurogenesis in brain tissue. In this study, PFOA at doses of 1, 5, 10, and 20 mg/kg were injected intraperitoneally into C57BL/6 J mice for 14 days, and the myelin content, CD4 + and CD8 + cell infiltration to brain regions were evaluated. Also, bromodeoxyuridine (BrdU) labeling was performed to compare neurogenesis among the groups. Luxol Fast Blue (LFB) staining revealed a significant decrease in myelin content in both sex at high concentrations (p < 0.001). The BrdU incorporation changes were observed in both sexes especially females which was highly related to the dose of PFOA and region of the brain. The infiltration rates of CD4 + and CD8 + cells to the brain were shown to be decreased; meanwhile the lymphocyte count was not significantly changed among groups over time and vice versa for the monocyte and neutrophils. Our results showed that PFOA had a negative impact on neurogenesis and the myelination process through the specific region of the brain depending on the dose and sex. Also, PFOA could disturb the number of CD4 + and CD8 + cells infiltrating the brain, which plays a crucial role in neurogenesis, leading to toxicity and neurological abnormalities. It seems that more research is needed to determine the exact mechanisms of PFOA neurotoxicity and its long-term behavioral consequences.
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14 August 2023
A Correction to this paper has been published: https://doi.org/10.1007/s00210-023-02630-2
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This study was supported by a grant (Project No. 199680) from Isfahan Pharmaceutical Science Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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AK and MAO conceived of the presented idea, AK and MK carried out the experiment, MS processed the results and prepared the manuscript, MAO supervise the project, all authors provided critical feedback and helped shape the research, analysis and manuscript.
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All procedures were approved by the Iran National Committee for Ethics in Biomedical Research (IR.MUI.RESEARCH.REC.1400.025) which was performed in accordance with the Guidelines for the Care and Use of Laboratory Animals.
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Neisiani, A.K., Mousavi, M.K., Soltani, M. et al. Perfluorooctanoic acid exposure and its neurodegenerative consequences in C57BL6/J mice. Naunyn-Schmiedeberg's Arch Pharmacol 396, 2357–2367 (2023). https://doi.org/10.1007/s00210-023-02387-8
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DOI: https://doi.org/10.1007/s00210-023-02387-8