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An Endogenous Ligand of Aryl Hydrocarbon Receptor 6-Formylindolo[3,2-b]Carbazole (FICZ) Is a Signaling Molecule in Neurogenesis of Adult Hippocampal Neurons

Abstract

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.

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Acknowledgments

The authors of this manuscript wish to express their appreciation to Shiraz University of Medical Sciences, Shiraz, Iran.

Funding

This work was supported by the Shiraz University of Medical Sciences grant for the accomplishment of the PhD thesis of Majid Keshavarzi (Grant number: 15168).

Author information

MK, MJK, AGB, and AMB participated in study design, data collection and evaluation, drafting, and statistical analysis. MK AGB and AMB conducted molecular experiments and RT qPCR analysis. All authors performed editing and approving the final version of this paper for submission.

Correspondence to Afshin Mohammadi-Bardbori.

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This article does not contain any studies with human participants performed by any of the authors. All experimental protocols were performed in accordance with the ethics committee guideline of the Shiraz University of Medical Sciences.

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Keshavarzi, M., Khoshnoud, M.J., Ghaffarian Bahraman, A. et al. An Endogenous Ligand of Aryl Hydrocarbon Receptor 6-Formylindolo[3,2-b]Carbazole (FICZ) Is a Signaling Molecule in Neurogenesis of Adult Hippocampal Neurons. J Mol Neurosci (2020). https://doi.org/10.1007/s12031-020-01506-x

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Keywords

  • Neurogenesis
  • AHR
  • Wnt/ß-catenin
  • FICZ
  • Learning and memory