Petersen S L, Curran M A, Marconi S A, Carpenter C D, Lubbers L S, McAbee M D
Department of Biology, Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Comp Neurol. 2000 Nov 20;427(3):428-39. doi: 10.1002/1096-9861(20001120)427:3<428::aid-cne9>3.0.co;2-p.
Dioxin exposure alters a variety of neural functions, most likely through activation of the arylhydrocarbon receptor (AhR) pathway. Many of the adverse effects, including disruption of circadian changes in hormone release and depressed appetite, seem to be mediated by hypothalamic and/or brainstem neurons. However, it is unclear whether these effects are direct or indirect, because there have been no comprehensive studies mapping the expression of components of the AhR pathway in the brain. Therefore, we used a sensitive in situ hybridization histochemical (ISHH) method to map the neural expression of AhR mRNA, as well as those of the mRNAs encoding the AhR dimerization partners, arylhydrocarbon receptor nuclear translocator (ARNT) and ARNT2. We found that AhR, ARNT, and ARNT2 mRNAs were widely distributed throughout the brain and brainstem. There was no neuroanatomic evidence that AhR is preferentially colocalized with ARNT or ARNT2. However, ARNT2, unlike ARNT expression, was relatively high in most regions. The most noteworthy regions in which we found AhR, ARNT, and ARNT2 mRNA were several hypothalamic and brainstem regions involved in the regulation of appetite and circadian rhythms, functions that are disrupted by dioxin exposure. These regions included the arcuate nucleus (Arc), ventromedial hypothalamus (VMH), paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN), nucleus of the solitary tract (NTS), and the dorsal and median raphe nuclei. This neuroanatomic information provides important clues as to the sites and mechanisms underlying the previously unexplained effects of dioxins in the central nervous system.
二噁英暴露会改变多种神经功能，很可能是通过激活芳烃受体（AhR）途径来实现的。许多不良反应，包括激素释放的昼夜节律变化紊乱和食欲减退，似乎是由下丘脑和/或脑干神经元介导的。然而，这些影响是直接的还是间接的尚不清楚，因为此前尚未有全面的研究来描绘AhR途径各组分在大脑中的表达情况。因此，我们采用了一种灵敏的原位杂交组织化学（ISHH）方法来描绘AhR mRNA以及编码AhR二聚体伴侣芳烃受体核转运蛋白（ARNT）和ARNT2的mRNA的神经表达情况。我们发现，AhR、ARNT和ARNT2 mRNA广泛分布于整个大脑和脑干。没有神经解剖学证据表明AhR优先与ARNT或ARNT2共定位。然而，与ARNT的表达不同，ARNT2在大多数区域的表达相对较高。我们发现AhR、ARNT和ARNT2 mRNA的最值得注意的区域是几个参与食欲和昼夜节律调节的下丘脑和脑干区域，而这些功能会因二噁英暴露而受到破坏。这些区域包括弓状核（Arc）、腹内侧下丘脑（VMH）、室旁核（PVN）、视交叉上核（SCN）、孤束核（NTS）以及背侧和中缝核。这一神经解剖学信息为二噁英在中枢神经系统中此前无法解释的作用的位点和机制提供了重要线索。
