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Research Paper|Volume 13, Issue 4|pp 5875—5891

Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression

Lei Gao1, Tingting Gao1, Ting Zeng1, Peng Huang1,2, Nai-Kei Wong3, Zhaoyang Dong4, Yunjia Li1, Guanghui Deng1, Zhiyong Wu1, Zhiping Lv1
  • 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
  • 2Foshan Maternal and Child Health Research Institute, Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China
  • 3State Key Discipline of Infectious Diseases, Shenzhen Third People’s Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, Guangdong, China
  • 4School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
* Equal contribution
Received: May 22, 2020Accepted: August 8, 2020Published: February 11, 2021
https://doi.org/10.18632/aging.202511

Copyright: © 2021 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Indoleamine 2, 3-dioxygenase 1 (IDO1) has been implicated in the pathogenesis of depression, though its molecular mechanism is still poorly understood. We investigated the molecular mechanism of IDO1 in depression by using the chronic unpredictable mild stress (CUMS) model in Ido1-/- mice and WT mice. The brain blood oxygen level dependent (BOLD) signals in mice were collected by functional magnetic resonance imaging (fMRI) technology. IDO1 inhibitor INCB024360 was intervened in dorsal raphe nucleus (DRN) through stereotactic injection. We found an elevation of serum IDO1 activity and decreased 5-HT in CUMS mice, and the serum IDO1 activity was negatively correlated with 5-HT level. Consistently, IDO1 was increased in hippocampus and DRN regions, accompanied by a reduction of hippocampal BDNF levels in mice with CUMS. Specifically, pharmacological inhibition of IDO1 activity in the DRN alleviated depressive-like behaviour with improving hippocampal BDNF expression and neurogenesis in CUMS mice. Furthermore, ablation of Ido1 exerted stress resistance and decreased the sensitivity of depression in CUMS mice with the stable BOLD signals, BDNF expression and neurogenesis in hippocampus. Thus, IDO1 hyperactivity played crucial roles in modulating 5-HT metabolism and BDNF function thereby impacting outcomes of hippocampal neurogenesis and BOLD signals in depressive disorder.