Inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cAMP-induced differentiation of rat C6 glial cell line

• Published in: Journal of neuroscience research 2001-05, Vol.64 (4), p.402-409
• Main Authors: Takanaga, Hiromi, Kunimoto, Manabu, Adachi, Tatsumi, Tohyama, Chiharu, Yasunobu Aoki
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; astrocyte; Astrocytes - drug effects; Astrocytes - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cyclic AMP - pharmacology; Cytochrome P-450 CYP1A1 - drug effects; Cytochrome P-450 CYP1A1 - metabolism; differentiation; dioxin; glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - drug effects; Glial Fibrillary Acidic Protein - metabolism; Molecular Sequence Data; Neuroglia - drug effects; Neuroglia - metabolism; Polychlorinated Dibenzodioxins - pharmacology; Rats; Receptors, Aryl Hydrocarbon - drug effects; Receptors, Aryl Hydrocarbon - metabolism; Teratogens - pharmacology
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.1091

Dioxin is suspected to cause adverse effects on the development of the central nervous system (CNS). To investigate the neurotoxic effects of dioxin on the differentiation of astrocytes, rat C6 glial cell line was used as a model, because these cells are induced to express astrocyte markers and to change the cell morphology toward an astrocytic phenotype by increasing intracellular cAMP levels. When C6 cells were simultaneously exposed to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and N6,O2′‐dibutylyl cAMP (dbcAMP), the expression of cytochrome P‐450 1A1 (CYP1A1) was dramatically increased, and the expression of aryl hydrocarbon receptor (AhR) was moderately decreased in a dose‐dependent manner. In addition, extension of astrocytic processes was inhibited by 1 nM TCDD that did not reduce cell viability. TCDD also inhibited the induction of glial fibrillary acidic protein (GFAP) expression in a dose‐dependent manner, until the end of a 72‐hr exposure period. This inhibition was restored by the addition of an antagonist of AhR, α‐naphthoflavone. These results indicate that TCDD inhibits astrocytic differentiation of C6 cells, which may be mediated by an AhR‐dependent pathway. J. Neurosci. Res. 64:402–409, 2001. © 2001 Wiley‐Liss, Inc.