2,3,7,8-tetrachlorodibenzo-p-dioxin alters hippocampal astroglia-neuronal gap junctional communication

Halogenated aromatic hydrocarbons (HAHs) such as dibenzo-p-dioxins are know n to alter cognitive function. However, the cellular basis of this disrupti on is not well understood. One possible deleterious effect of exposure to H AHs could be on gap junctional intercellular communication (GJIC) between n eurons and astroglia in the brain. As such, this study examined the effects of the highly toxic prototypic HAH; 2,3,7,8-tetrachlorodibenzo-p-dioxin (T CDD) on GJIC in rat hippocampal primary cell culture. Initial measurements of fluorescence recovery after photobleaching (gap-FRAP) showed dye transfe r between astroglia and neurons. N-octanol, a lipophilic alcohol known to u ncouple cells by decreasing the open probability of gap junctional channels blocked astroglial-neuronal(A-A) communication as well as astroglial-astro glial (A-A) communication. TCDD initially downregulated GJIC between neuron s and astroglia of treatment, but had no effect on astroglial cell pairs. T hese results indicate the presence of GJIC between neurons and astroglia in culture and demonstrate different sensitivities of gap junction responses to TCDD in homologous and heterologous cell pairs. The finding that 2,3,7,8 -TCDD disrupts GJIC through A-N but not A-A channels may have important imp lications for impaired brain function resulting from developmental exposure to TCDD. (C) 2000 Inter Press Inc.