Neurogenesis is a dynamic and physiologic developmental process that affects learning and hippocampal dependent memory. It is regulated by multi-cellular micro-environment and different types of transcription factors. The neurogenesis effects of endogenously activated aryl hydrocarbon receptor (AHR) by its endogenous ligand, 6-formylindolo[3,2-b] carbazole (FICZ), and its interactions with the Wnt/β-catenin signaling pathway were the main purpose of this study. In accordance, learning and hippocampus-dependent memory were examined. Male BALB/C mice received FICZ, CH223191, and XAV-939 in a single dose of 100 μg/kg, 1 mg/kg, and 5 mg/kg of body weight respectively via intraperitoneal (IP) injection. qRT-PCR for gene analyses and protein assay on the 7th and 28th days were performed. To assess the hippocampal dependent memory, they also underwent contextual fear conditioning on the 28th day after treatment. Our results showed that FICZ treatment led to elevation of the proneural transcription factors ASCL1 and Ngn2, immature neural marker DCX, differentiation neurons marker, NeuN, as well as β-catenin at mRNA and protein levels. We also indicated that hippocampal dependent memory and learning task were improved by FICZ treatment and impaired by the AHR and Wnt/ß-catenin inhibition. In this study for the first time, we demonstrated that the endogenous ligand of AHR, FICZ, has a positive effect on short- and long-term memory as well as learning skills. This ability is possibly mediated by the AHR-Wnt/ß-catenin cross-talk.

中文翻译：

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芳烃受体6-甲酰基吲哚[3,2-b]咔唑（FICZ）的内源性配体是成人海马神经元神经发生的信号分子。

神经发生是影响学习和海马依赖性记忆的动态和生理发育过程。它受多细胞微环境和不同类型的转录因子的调控。其内源性配体6-甲酰基吲哚并[3,2-b]咔唑（FICZ）对内源性活化芳烃受体（AHR）的神经发生作用及其与Wnt /β-catenin信号通路的相互作用是其主要目的。研究。因此，检查了学习和海马依赖性记忆。雄性BALB / C小鼠通过腹膜内（IP）注射分别以100μg/ kg，1 mg / kg和5 mg / kg体重的单剂量接受FICZ，CH223191和XAV-939。在第7天和第28天进行qRT-PCR进行基因分析和蛋白质测定。为了评估海马依赖性记忆，在治疗后的第28天，他们还进行了情境恐惧调节。我们的结果表明，FICZ治疗导致proneural转录因子ASCL1和Ngn2升高， mRNA和蛋白质水平的未成熟神经标记物DCX，分化神经元标记物，NeuN以及β-连环蛋白。我们还表明，通过FICZ治疗可改善海马依赖性记忆和学习任务，并受到AHR和Wnt /β-catenin抑制作用的损害。在这项研究中，我们首次证明AHR的内源性配体FICZ对短期和长期记忆以及学习技能具有积极作用。此功能可能是由AHR-Wnt /β-catenin串扰介导的。