Effects of 50-Hz magnetic field and bisphenol A exposure on phosphorylation of Tau protein in rat brain tissue and Neuro-2a cells

Abstract

Objective To investigate the effects of 50-Hz magnetic field and bisphenol A (BPA) alone or combined exposure on the phosphorylation of Tau protein in nerve cells. Methods A total of 24 SD male rats (body weight 150±10 g) were randomly and equally divided into 4 groups: control group (normal saline gavage+magnetic field sham-exposure), 50-Hz magnetic field exposure group (0.5 mT, 50 Hz magnetic field exposure 4 h/d+normal saline gavage), BPA exposure group (BPA 20 μg·kg-1·d-1 gavage+ magnetic field sham-exposure), and combined exposure group (BPA 20 μg·kg-1·d-1 gavage+0.5 mT, 50 Hz magnetic field exposure 4 h/d). The magnetic field exposure was performed once per day, 6 days per week, for consecutive 12 weeks. The protein expression of Tau-Thr231 and Tau-Ser404, as well as cell apoptosis in frozen slices of cerebral cortex and hippocampus were detected by immunohistofluorescence assay and TUNEL assay, respectively. For cell experiments, Neuro-2a cells were exposed to 50 Hz magnetic field (1.0 mT, 48 h), BPA treatment (100 μmol/L, 24 h), as well as combined exposure (50 Hz magnetic field+BPA), respectively. Cell viability was tested by CCK-8 assay, and the protein expression of Tau-Thr231, Tau-Ser404 and Caspase-3 were measured using immunofluorescence assay and Western blotting. Results As compared with the control group, the phosphorylation of Tau-Thr231 was significantly increased in cerebral cortex and hippocampus of rats after 12 weeks of 50 Hz magnetic field exposure (P < 0.05). The Tau-Thr231 phosphorylation in rat cerebral cortex and hippocampus and the Tau-Ser404 phosphorylation in cerebral cortex were remarkably elevated after 12 weeks of BPA exposure alone or in combination with 50 Hz magnetic field (P < 0.05). The co-exposure also induced obvious neuronal apoptosis in cerebral cortex and hippocampus of rats (P < 0.05). For cell experiments, the Neuro-2a cell viability was greatly lowered after exposure to 50 Hz magnetic field, BPA alone or combined treatment for 48 h (P < 0.05). The Tau-Ser404 phosphorylation was notably up-regulated (P < 0.05) after 50 Hz magnetic field exposure; the phosphorylation of Tau-Thr231 and Tau-Ser404, as well as the expression of Caspase-3 were also enhanced (P < 0.05) after BPA exposure or co-exposure. Conclusion Exposure to 50 Hz magnetic field and/or BPA can induce hyperphosphorylation of Tau protein at different amine acid site, and there are synergistic effects between the 2 exposures, which may cause nerve cell damage.

Keywords

• 50 hz magnetic field
• bisphenol a
• male rats
• neuro-2a cells
• tau phosphorylation