Student Jeju National University, Cheju-do, Republic of Korea
Abstract: Bisphenol A (BPA), an industrial chemical commonly found in food and water containers as well as various consumer products, acts as an endocrine disruptor due to its estrogen-mimicking properties. BPA exposure leads to its accumulation in the brain, resulting in mitochondrial dysfunction, including increased mitochondrial reactive oxygen species (mtROS) production and dysregulated mitophagy. This study investigated how these disruptions alter exosome secretion of fragmented mitochondria and contribute to neurodegenerative phenotypes. Initially, we observed in the human neuroblastoma cell line SH-SY5Y that high-dose BPA exposure (100 μM) augmented mtROS and mitophagy, which could be regulated by the abatement of membrane estrogen receptor (ER) activity. Notably, BPA significantly enhanced exosome secretion containing mitochondrial fragments, evidenced by elevated levels of TOMM20 and mitochondrial RNAs related to oxidative phosphorylation (ND1-ND6, COX1-COX4) in SH-SY5Y cells. However, BPA reduced exosome secretion from the mouse hippocampal neuronal cell line HT-22 and primary microglia, which was increased in mouse primary astrocytes. In a co-culture system between mouse primary astrocytes and HT-22 cells, BPA increased mitochondrial secretion into the media from HT-22 cells, which were subsequently absorbed by astrocytes. Additionally, BPA exposure significantly elevated GFAP protein levels in astrocytes, indicating astrocytic activation. In conclusion, these findings suggest that BPA increases mitochondrial secretion via exosomes, thereby diminishing mitochondrial content in neurons and contributing to neurodegeneration.
