Interaction of the immune-inflammatory and the kynurenine pathways in rats resistant to antidepressant treatment in model of depression

Duda, Weronika; Curzytek, Katarzyna; Kubera, Marta; Connor, Thomas J.; Fagan, E.M.; Basta‐Kaim, Agnieszka; Trojan, Ewa; Papp, Mariusz; Gruca, Piotr; Budziszewska, Bogusława; Leśkiewicz, Monika; Maes, Michaël; Lasoń, Władysław

doi:10.1016/j.intimp.2019.05.039

Cited by 20 publications

(17 citation statements)

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“…However, Laugeray et al ( 2010 ) observed that mice subjected to unpredictable CMS exhibit a reduced level of kynurenic acid in the amygdala and striatum. Similarly, CMS caused a downregulation of KatII mRNA expression in the cortex (Duda et al 2019 ). These differences may be related to the fact that the analysed studies used a variety of biological material, including human, mouse and rat tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Since the activity of the Kmo gene is associated with the production of neurotoxic 3-hydroxykynurenine and quinolinic acid and the generation of reactive oxygen species, the observed elevated methylation level might contribute to the reduction in Kmo activity and the impairment of neurons after venlafaxine administration (Guillemin 2012 ; Colin-Gonzalez et al 2013 ). Moreover, the CMS procedure increased the mRNA expression level of Kmo in the cortex and may be associated with a higher level of the excitotoxic compound (Duda et al 2019 ). However, Wang et al ( 2018 ) found that rats subjected to the chronic unpredictable mild stress procedure exhibited diminished concentrations and reduced activity of Kmo in the plasma.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

et al. 2020

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A growing body of evidence suggests that depression may be associated with impairment of the tryptophan catabolites (TRYCATs) pathway. The present study investigated the effects of the chronic administration of venlafaxine on the expression and methylation status of Katl, Tph1/2, Ido1, Kmo and Kynu in the brain and blood of rats exposed to the CMS model of depression. The rats were subjected to the CMS procedure for 2 or 7 weeks and administered venlafaxine (10 mg/kg/day, IP) for 5 weeks. mRNA and protein expression and the methylation status of gene promoters in PBMCs and six brain structures were evaluated and analysed using the TaqMan Gene Expression Assay and Western blotting, and methylation-sensitive high-resolution melting (MS-HRM), respectively. We found that the CMS procedure increased KatI expression in the midbrain and KatII expression in the midbrain and the amygdala, while venlafaxine administration decreased KatII expression in the hypothalamus and the cerebral cortex. The methylation status of the Tph1 and Kmo promoters in peripheral blood mononuclear cells (PBMCs) was significantly increased in the stressed group after antidepressant therapy. The protein levels of Tph1 and Ido1 were decreased following venlafaxine administration. Our results confirmed that CMS and venlafaxine modulate the expression levels and methylation status of genes involved in the TRYCATs pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

et al. 2020

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“…Another recent study showed decreased IDO1 and KMO expression in the murine brain as well as decreased IDO1 and IDO2 expression in human peripheral blood mononuclear cells as a consequence of antidepressant treatment (244,245). This, in turn, demonstrates that reduction of psychosocial stress can also reduce inflammation-related factors.…”

Section: Inhibition Of Tryptophan Breakdown For Treatment Of Fatigue mentioning

confidence: 92%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

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“…On the other hand, Wang et al (2018) observed no differences in Kmo activity between control and chronic unpredictable mild stress groups [ 49 ]. In the case of KatII, CMS caused a downregulation of mRNA expression in the cortex [ 50 ]. On the other hand, we observed that chronic administration of agomelatine for five weeks led to an increase in the KatII protein expression in the hippocampus, hypothalamus, and amygdala of rats stressed for seven weeks.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures

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Synowiec

Jóźwiak

et al. 2020

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Depression is the serious mental disorder. Previous studies suggest that the development mechanism of depression may be associated with disorders of the tryptophan catabolic pathway (TRYCAT). Thus, this study investigates the effect of agomelatine treatment on the expression and methylation status of genes involved in TRYCAT in the brain and blood of rats exposed to a chronic mild stress (CMS). Separate groups of rats were exposed to CMS for two or seven weeks; the second group received vehicle or agomelatine for five weeks. After completion of both stress conditions and treatment, the expression levels of messenger RNA (mRNA) and protein, as well as the methylation status of promoters, were measured in peripheral blood mononuclear cells (PBMCs) and in brain structures with the use of TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques. In PBMCs, Kmo mRNA expression increased in the group after CMS, while this effect was normalized by agomelatine therapy. In brain, KatI and KatII expression changed following CMS exposure. Moreover, CMS decreased the methylation status of the second Tdo2 promoter in the amygdala. Protein expression of Tph1, Tph2, Ido1, and KatII changed in the group after CMS and agomelatine administration, most prominently in the basal ganglia, cerebral cortex, hippocampus, and amygdala. The results indicate that CMS and agomelatine affect the mRNA and protein expression, as well as the methylation of promoters of genes involved in the tryptophan catabolic pathway.

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Interaction of the immune-inflammatory and the kynurenine pathways in rats resistant to antidepressant treatment in model of depression

Cited by 20 publications

References 59 publications

The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures

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