Astrocytes Respond to Environment-Relevant Doses TCDD in a Specific Manner Which Is Different from the Endogenous AhR Ligand (FICZ)

Abstract

Astrocytes play an important role in the nervous system’s response to external stimulation. Environmental pollutants could activate astrocytes into A1 (toxic) or A2 (protective) types and induce different effects. Meanwhile, the aryl hydrocarbon receptor (AhR) is an environmental molecule sensor in the body and has various ligands. But the difference between exogenous and endogenous AhR ligands on the astrocytic activation is unclear; in this study, we employed rat primary cultured cortical astrocytes to reveal the effects and mechanisms of AhR ligands on astrocytic activation. We found that, after treatment with exogenous AhR ligand (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) ranging from 0.01 to 0.1 nmol/L, astrocytes mainly exhibited A2 type activation. The specific manifestation includes the increase in the expression of A2 marker genes, the enhancement of cellular autonomous movement, the expression and secretion of chemokines, such as Cxcl10, Cxcl2, and Ccl7. And TCDD-induced A2 type astrocytes show a positive impact on neuronal synaptic formation. Although both TCDD and endogenous AhR ligand (6-formylindolo[3,2-b] carbazole, FICZ) could activate AhR pathway in astrocytes, FICZ (50 nmol/L) neither induces activation of A2 type astrocytes nor upregulation of chemokines. Therefore, our findings suggest that AhR is crucial for astrocytes to recognize environmental pollutants and protect the nervous system.