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

Gao, Lei1; Gao, Tingting1; Zeng, Ting1; Huang, Peng1,2; Wong, Nai-Kei3; Dong, Zhaoyang4; Li, Yunjia1; Deng, Guanghui1; Wu, Zhiyong1; Lv, Zhiping1

2021-02-28

Aging-US   影响因子和分区

1945-4589

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 behaviors 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.

depression IDO1 dorsal raphe nucleus neurogenesis blood oxygen level-dependent signal

SCI

英语

其他

National Natural Science Foundation of China[81230085,81873170,82004091,81703926] ; Natural Science Foundation of Guangdong Province["2018B030306012","2017A030310289"] ; Department of education of Guangdong Province-Project for young innovation talents[2017KQNCX043] ; Traditional Chinese Medicine of Guangdong Province[20201089]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:000624694000004

IMPACT JOURNALS LLC

Web of Science

1.Southern Med Univ, Sch Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China
2.Southern Med Univ, Foshan Maternal & Child Hlth Res Inst, Affiliated Hosp, Foshan, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, State Key Discipline Infect Dis, Hosp Affiliated 2, Shenzhen, Guangdong, Peoples R China
4.Guangzhou Univ Chinese Med, Sch Nursing, Guangzhou, Guangdong, Peoples R China

Gao, Lei,Gao, Tingting,Zeng, Ting,et al. Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression[J]. Aging-US,2021,13(4).

Gao, Lei.,Gao, Tingting.,Zeng, Ting.,Huang, Peng.,Wong, Nai-Kei.,...&Lv, Zhiping.(2021).Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression.Aging-US,13(4).

Gao, Lei,et al."Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression".Aging-US 13.4(2021).