A comprehensive review of the neurobehavioral effects of bisphenol S and the mechanisms of action: New insights from in vitro and in vivo models

The normal brain development and function are delicately driven by an ever-changing milieu of steroid hormones arising from fetal, placental, and maternal origins. This reliance on the neuroendocrine system sets the stage for the exquisite sensitivity of the central nervous system to the adverse effects of endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA) is one of the most common EDCs which has been a particular focus of environmental concern for decades due to its widespread nature and formidable threat to human and animal health. The heightened regulatory actions and the scientific and public concern over the adverse health effects of BPA have led to its replacement with a suite of structurally similar but less known alternative chemicals. Bisphenol S (BPS) is the main substitute for BPA that is increasingly being used in a wide array of consumer and industrial products. Although it was considered to be a safe BPA alternative, mounting evidence points to the deleterious effects of BPS on a wide range of neuroendocrine functions in animals. In addition to its reproductive toxicity, recent experimental efforts indicate that BPS has a considerable potential to induce neurotoxicity and behavioral dysfunction. This review analyzes the current state of knowledge regarding the neurobehavioral effects of BPS and discusses its potential mode of actions on several aspects of the neuroendocrine system. We summarize the role of certain hormones and their signaling pathways in the regulation of brain and behavior and discuss how BPS induces neurotoxicity through interactions with these pathways. Finally, we review potential links between BPS exposure and aberrant neurobehavioral functions in animals and identify key knowledge gaps and hypotheses for future research.