Gap Junction Protein Connexin 43 as a Target Is Internalized in Astrocyte Neurotoxicity Caused by Di-(2-ethylhexyl) Phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastic products, consumer products, and packaging materials. It is of great health concern in both animals and humans as it released into the environment and entered into the body from plastic products over time, thereby resulting in neurotoxicity. As a pivotal regulator of the central nervous system (CNS), astrocytes, are crucial for maintaining brain homeostasis. Nevertheless, the underlying reason for astrocyte neurotoxicity due to DEHP exposure remains incompletely understood. Here, using an in vivo model of neurotoxicity in quail, this study summarizes that Cx43 is internalized by phosphorylation and translocated to the nucleus as a consequence of DEHP exposure in astrocytes. This study further demonstrated that astrocytes transformed to pro-inflammatory status and induced the formation of autophagosomes. Of note, integrated immunofluorescent codetection approaches revealed an overexpression of the glial fibrillary acidic protein (GFAP) and down-expression of Cx43 in astrocytes. Therefore, in terms of neurotoxicity, this experiment in vivo models directly linked Cx43 internalization to autophagy and neuroinflammation and ultimately locked these changes to the astrocytes of the brain. These findings unveil a potential approach targeting Cx43 internalization for the treatment of neurodegeneration caused by DEHP exposure in astrocytes.