Open AccessBisphenol-A impairs synaptic formation and function by RGS4-mediated regulation of BDNF signaling in the cerebral cortex
Author(s) -
Sung-Ae Hyun,
Moon Yi Ko,
Sumi Jang,
ByoungSeok Lee,
Jaerang Rho,
Kee K. Kim,
Woo Yang Kim,
Minhan Ka
Publication year - 2022
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.049177
Subject(s) - neuroscience , neurotransmission , synapse , endocrine disruptor , dendritic spine , bisphenol a , endocrine system , excitatory postsynaptic potential , prefrontal cortex , cerebral cortex , biology , medicine , endocrinology , chemistry , inhibitory postsynaptic potential , cognition , hippocampal formation , hormone , receptor , organic chemistry , epoxy
Bisphenol-A (BPA) is a representative endocrine disruptor, widely used in a variety of products including plastics, medical equipment and receipts. Hence, most people are exposed to BPA via the skin, digestive system or inhalation in everyday life. Furthermore, BPA crosses the blood-brain barrier and is linked to multiple neurological dysfunctions found in neurodegenerative and neuropsychological disorders. However, the mechanisms underlying BPA-associated neurological dysfunctions remain poorly understood. Here, we report that BPA exposure alters synapse morphology and function in the cerebral cortex. Cortical pyramidal neurons treated with BPA showed reduced size and number of dendrites and spines. The density of excitatory synapses was also decreased by BPA treatment. More importantly, we found that BPA disrupted normal synaptic transmission and cognitive behavior. RGS4 and its downstream BDNF/NTRK2 pathway appeared to mediate the effect of BPA on synaptic and neurological function. Our findings provide molecular mechanistic insights into anatomical and physiological neurotoxic consequences related to a potent endocrine modifier.