Kimura Eiki
Department of Environmental Health, University of Fukui School of Medical Sciences, 23-3 Matsuoka-shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
Toxics. 2025 Jul 16;13(7):596. doi: 10.3390/toxics13070596.
Industrial development has increased environmental dioxin concentrations, sparking concern about human health impacts. Examining dioxin neurotoxicity has highlighted associations with cognitive impairment and behavioral abnormality. Dioxins are ligands of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor; it is speculated that dioxin-induced AHR activation is pivotal for toxic effects. Accurate AHR-expressing cell identification is therefore indispensable for understanding the molecular and cellular mechanisms of dioxin toxicity. Herein, current knowledge regarding AHR expression in the mammalian brain is summarized, and dioxin neurotoxicity mechanisms are discussed. Histological studies show AHR-expressing neurons in multiple brain regions, including the hippocampus and cerebral cortex. Dopaminergic and noradrenergic neurons exhibit AHR expression, suggesting possible roles in the monoaminergic system. AHR overactivation evokes dendritic arborization atrophy, whereas its deficiency increases complexity, implying that AHR-mediated signaling is crucial for neuronal growth and maturation. AHR is also involved in neurogenesis and neuronal precursor migration. Collectively, these findings support the notion that dioxin-induced AHR overactivation in individual neurons disrupts neural circuit structure, ultimately leading to impaired brain function. However, as AHR downstream signaling is intertwined with various molecules and pathways, the precise mechanisms remain unclear. Further studies on the expression, signaling, and roles of AHR are needed to clarify dioxin neurotoxicity.
工业发展增加了环境中二噁英的浓度，引发了对人类健康影响的担忧。对二噁英神经毒性的研究突出了其与认知障碍和行为异常的关联。二噁英是芳烃受体（AHR）的配体，AHR是一种配体激活的转录因子；据推测，二噁英诱导的AHR激活对于毒性作用至关重要。因此，准确鉴定表达AHR的细胞对于理解二噁英毒性的分子和细胞机制不可或缺。本文总结了目前关于AHR在哺乳动物大脑中表达的知识，并讨论了二噁英神经毒性机制。组织学研究表明，在包括海马体和大脑皮层在内的多个脑区存在表达AHR的神经元。多巴胺能和去甲肾上腺素能神经元表现出AHR表达，提示其在单胺能系统中可能发挥作用。AHR过度激活会引发树突分支萎缩，而其缺乏则会增加树突分支的复杂性，这意味着AHR介导的信号传导对于神经元的生长和成熟至关重要。AHR还参与神经发生和神经元前体迁移。总的来说，这些发现支持这样一种观点，即二噁英诱导的单个神经元中AHR过度激活会破坏神经回路结构，最终导致脑功能受损。然而，由于AHR下游信号与各种分子和途径相互交织，其确切机制仍不清楚。需要进一步研究AHR的表达、信号传导和作用，以阐明二噁英神经毒性。
