Distribution of mRNAs encoding the arylhydrocarbon receptor, arylhydrocarbon receptor nuclear translocator, and arylhydrocarbon receptor nuclear translocator-2 in the rat brain and brainstem

Dioxin exposure alters a variety of neural functions, most likely through a ctivation of the arylhydrocarbon receptor (AhR) pathway. Many of the advers e effects, including disruption of circadian changes in hormone release and depressed appetite, seem to be mediated by hypothalamic and/or brainstem n eurons. However, it is unclear whether these effects are direct or indirect , because there have been no comprehensive studies mapping the expression o f components of the AhR pathway in the brain. Therefore, we used a sensitiv e in situ hybridization histochemical (ISHH) method to map the neural expre ssion of AhR mRNA, as well as those of the mRNAs encoding the AhR dimerizat ion partners, arylhydrocarbon receptor nuclear translocator (ARNT) and ARNT 2. We found that AhR, ARNT, and ARNT2 mRNAs were widely distributed through out the brain and brainstem,:There was no neuroanatomic evidence that AhR i s preferentially colocalized with ARNT or ARNT2. However, ARNT2, unlike ARN T expression, was relatively high in most regions. The most noteworthy regi ons in which we found AhR, ARNT, and ARNT2 mRNA were several hypothalamic a nd brainstem regions involved in the regulation of appetite and circadian r hythms, functions that are disrupted by dioxin exposure. These regions incl uded the arcuate nucleus (Arc), ventromedial hypothalamus (VMH), paraventri cular nucleus (PVN), suprachiasmatic nucleus (SCN), nucleus of the solitary tract (NTS), and the dorsal and median raphe nuclei. This neuroanatomic in formation provides important clues as to the sites and mechanisms underlyin g the previously unexplained effects of dioxins in the central nervous syst em. (C) 2000 Wiley-Liss, Inc.