Bisphenol S (BPS), the most common substitute for
bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the
BDNF-TrkB-CREB (
brain-derived neurotrophic factor-
tropomyosin-related
kinase B-
CAMP response element-binding protein) signalling pathway in
bisphenol S-induced neurotoxicity via methylation regulation in male C57BL/6 mice. The mice were treated with
sesame oil or 2, 20 and 200 mg/kg
body weight BPS for 28 consecutive days, and the hippocampus was extracted. We recorded the
body weight, organ index, and hippocampal pathology and ultrastructure of the mice. The
BDNF, TrkB, CREB, phosphorylated (p)-CREB, DNMTs (
DNA methyltransferases) levels were determined by qRT-PCR and/or Western blotting.
BDNF promoter IV methylation level was detected by
bisulfite sequencing PCR. BPS damaged the mouse hippocampus ultrastructure and reduced the number of synapses. Further, it increased the methylation rate of
BDNF promoter IV; downregulated
BDNF, CREB, p-CREB/CREB and DNMT1 expression; and upregulated DNMT3a and DNMT3b expression. Therefore, we speculate that the
BDNF-TrkB-CREB pathway may be involved in BPS-induced neurotoxicity in male mice by regulating methylation.