Dataset Information

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

ABSTRACT:

Background

The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association.

Methods

According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay.

Results

Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014).

Conclusions

Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

SUBMITTER: Chen H

PROVIDER: S-EPMC9998486 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Chen Hengshu H Huang Xia X Zeng Chang C Sun Dongren D Liu Fan F Zhang Jingyuan J Liao Qiao Q Luo Shihang S Xu Weiye W Xiao Yeqing Y Zeng Danfeng D Song Mingyu M Tian Fafa F

Frontiers in immunology 20230224

<h4>Background</h4>The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association.<h4>Methods</h4>According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and it ...[more]

PMID: 36911716

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Project description:Male meiotic germ cell including the spermatozoa represent a great challenge to the immune system, as they appear long after the establishment of normal immune tolerance mechanisms. The capacity of the testes to tolerate autoantigenic germ cells as well as survival of allogeneic organ engrafted in the testicular interstitium have led to consider the testis an immunologically privileged site. Disruption of this immune privilege following trauma, tumor, or autoimmune orchitis often results in male infertility. Strong evidence indicates that indoleamine 2,3-dioxygenase (IDO) has been implicated in fetal and allograft tolerance, tumor immune resistance, and regulation of autoimmune diseases. IDO and tryptophan 2,3-dioxygenase (TDO) catalyze the same rate-limiting step of tryptophan metabolism along a common pathway, which leads to tryptophan starvation and generation of catabolites collectively known as kynurenines. However, the relevance of tryptophan metabolism in testis pathophysiology has not yet been explored. Here we assessed the in vivo role of IDO/TDO in experimental autoimmune orchitis (EAO), a model of autoimmune testicular inflammation and immunologically impaired spermatogenesis. EAO was induced in adult Wistar rats with testicular homogenate and adjuvants. Control (C) rats injected with saline and adjuvants and normal untreated rats (N) were also studied. mRNA expression of IDO decreased in whole testes and in isolated Sertoli cells during EAO. TDO and IDO localization and level of expression in the testis were analyzed by immunostaining and Western blot. TDO is expressed in granulomas from EAO rats, and similar protein levels were observed in N, C, and EAO groups. IDO was detected in mononuclear and endothelial cells and reduced IDO expression was detected in EAO group compared to N and C rats. This phenomenon was concomitant with a significant reduction of IDO activity in EAO testis measured by tryptophan and kynurenine concentrations (HPLC). Finally, in vivo inhibition of IDO with 1-methyl-tryptophan increased severity of the disease, demonstrating down regulation of IDO-based tolerance when testicular immune regulation was disrupted. We present evidence that an IDO-based mechanism is involved in testicular immune privilege.

Project description:BackgroundPost-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD.MethodsA total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data were collected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity.ResultsDepressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region.ConclusionsThere are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDS severity.Trial registrationURL: http://www.chictr.org.cn/enIndex.aspx ; Unique identifier: ChiCTR-ROC-17013993.

Dataset Information

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Background

Methods

Results

Conclusions

Publications

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

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