Bisphenol S and F disrupt cerebellar functions and neuronal health: The role of estrogen receptor and BMP2 signaling.

Bisphenol S (BPS) and bisphenol F (BPF) have gained attention as endocrine disruptors that affect brain functions, with their specific impact on the cerebellum being less thoroughly explored. Estrogen receptors (ERs) are crucial in maintaining neuronal health in the cerebellum, which participates in motor coordination. Additionally, bone morphogenetic proteins (BMPs) participate in various neuronal processes and are influenced by ER signaling. This study investigated how environmentally relevant doses of BPS and BPF (0.4-40 μg/kg) affect cerebellar functions in adult female rats, with a particular emphasis on ER and BMP signaling. Our assessments of motor coordination, conducted using rota-rod and grip strength tests, indicated that exposure to BPS/BPF significantly compromised balance and muscle strength. Investigation of cerebellar tissue revealed decreased levels of estrogen receptors ERα and ERβ, along with reduced BMP2 at both mRNA and protein levels. BMP2 signaling was also diminished, marked by lower BMPR2 and downstream components like p-Smad. Notably, ER agonists PPT and DPN restored BMP2 levels, while BMP2 administration enhanced ERα and ERβ levels, highlighting a reciprocal relationship between these signaling pathways. Moreover, treatments with PPT, DPN, and BMP2 led to improvements in neuronal survival, NeuN levels, and overall motor coordination performance. In conclusion, BPS and BPF disrupt cerebellar functions and neuronal health by interfering with the interplay between ER and BMP2 signaling, suggesting that targeting these pathways may help mitigate the adverse effects of these chemicals.