Resolution of inflammation and mood disorders

Chistyakov, Dmitry V.; Astakhova, A. A.; Sergeeva, Marina G.

doi:10.1016/j.yexmp.2018.08.002

Cited by 34 publications

(34 citation statements)

References 202 publications

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“…Oxylipins may be other suspected substances for transmitting information from tolerant cells to naive ones. This class of substances includes both pro-inflammatory compounds and resolution substances, which are responsible for restoring the system after the pro-inflammatory stimulus has been applied [1,5]. Although COX-2 expression was used as a classic marker of inflammation for a long time, oxylipins were typically evaluated in one or two compounds.…”

Section: Discussionmentioning

confidence: 99%

“…A prominent example is the inducible cyclooxygenase 2 (COX-2), a key enzyme of eicosanoid biosynthesis. Its products, i.e., prostaglandins, show both pro-inflammatory and pro-resolving qualities [5,15,16]. Our recent studies revealed the complex regulation of COX-2 expression both at the transcriptional and post-transcriptional levels in primary rat astrocytes [12][13][14].…”

mentioning

confidence: 86%

“…Neuroinflammation underlies the pathology of neurological disorders, such as multiple sclerosis, and contributes to other neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as other brain pathologies, including post-ischemic neurodegeneration, and traumatic, metabolic, toxic, and neoplastic disturbances [5][6][7]. Astrocytes are immunocompetent cells of the nervous tissue which play an essential role in neuroinflammation [5,6,8,9], sense LPS signals and promptly respond to pro-inflammatory challenges by activation of downstream signaling cascades, including conventional markers of inflammation: IL-6, TNFα, COX-2 etc. [6,[10][11][12][13][14].…”

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confidence: 99%

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Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

Chistyakov

Astakhova

Azbukina

et al. 2019

Cells

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A phenomenon of endotoxin tolerance where prior exposure of cells to minute amounts of lipopolysaccharide (LPS) causes them to become refractory to a subsequent high-amount endotoxin challenge is well described for innate immune cells such as monocytes/macrophages, but it is still obscure for brain cells. We exposed primary rat cortical astrocytes to a long-term low-grade concentration of LPS, followed by stimulation with a middle-grade concentration of LPS. Inflammatory markers, i.e., pro-inflammatory cytokine TNFα, inducible enzymes COX-2 and iNOS, anti-inflammatory cytokine interleukin 10 (IL-10) detected at the mRNA and protein levels reveal similarities between astrocytes and macrophages in the model, i.e., tolerance in pro-inflammatory markers and priming in IL-10. Long-term or short-term treatment with IL-10 does not change cell sensitivity for LPS, which makes doubtful its involvement in the mechanisms of cell tolerance development. Significant changes occur in the oxylipin profiles measured by UPLC-MS/MS analysis. The priming occurs in the following compounds: 11-HETE, PGD 2 , PGE 2 , cyclopentenone prostaglandins, and TXB 2 . Tolerance is observed for 12-HHT, PGF 2α , and 6-keto-PGF 1α . As far as we know, this is the first report on changes in oxylipin profiles in the endotoxin tolerance model. The data can greatly improve the understanding of oxylipins' role in inflammatory and resolution processes in the brain and mechanisms of astrocyte involvement in neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 86%

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confidence: 99%

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Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

Chistyakov

Astakhova

Azbukina

et al. 2019

Cells

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“…The conversion of PUFAs into oxylipins occurs via three major pathways, involving cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 monooxygenases (CYP450) [5]. This class of substances includes both pro-inflammatory compounds and resolution substances, which are responsible for restoring the system after the pro-inflammatory stimulus has been applied [3,6]. There are limited data on the relationship between oxylipins and various cell polarization and/or adaptation states.…”

Section: Introductionmentioning

confidence: 99%

“…These cells fulfill an important role as innate immune cells in the brain [19]. As a regulator of brain inflammation, astrocytes can release various immune and inflammatory mediators, such as pro-and anti-inflammatory cytokines/chemokines and oxylipins, which may subsequently exert neurotoxic or neuroprotective effects [6,12,15]. Astrocytes sense lipopolysaccharide (LPS) signals via the signaling system of Toll-like receptors (TLRs) and promptly respond to pro-inflammatory challenges posed by the activation of downstream signaling cascades, including conventional markers of inflammation: interleukin 6 (IL-6), Tumor necrosis factor alpha (TNFα), COX-2, and CC chemokines [11,20,21].…”

Section: Introductionmentioning

confidence: 99%

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

Chistyakov

Gavrish

Goriainov

et al. 2020

IJMS

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Functional phenotypes, which cells can acquire depending on the microenvironment, are currently the focus of investigations into new anti-inflammatory therapeutic approaches. Glial cells, microglia, and astrocytes are major participants in neuroinflammation, but their roles differ, as microglia are cells of mesodermal origin, while astrocytes are cells of ectodermal origin. The inflammatory phenotype of cells can be modulated by ω-6- and ω-3-polyunsaturated fatty acid-derived oxylipins, although data on changes in oxylipin profiles in different cell adaptations to pro- and anti-inflammatory stimuli are scarce. Our study aimed to compare UPLC-MS/MS-measured oxylipin profiles in various rat astrocyte adaptation states. We used cells treated for 24 h with lipopolysaccharide (LPS) for classical pro-inflammatory adaptation and with interleukin 4 (IL-4) or 10 (IL-10) for alternative anti-inflammatory adaptation, with the resulting phenotypes characterized by quantitative real-time PCR (RT-PCR). We also tested long-term, low-concentration LPS treatment (endotoxin treatment) as a model of astrocyte adaptations. The functional response of astrocytes was estimated by acute (4 h) LPS-induced cell reactivity, measured by gene expression markers and oxylipin synthesis. We discovered that, as well as gene markers, oxylipin profiles can serve as markers of pro- (A1-like) or anti-inflammatory (A2-like) adaptations. We observed predominant involvement of ω-6 polyunsaturated fatty acid (PUFA) and the cyclooxygenase branch for classical (LPS) pro-inflammatory adaptations and ω-3 PUFA and the lipoxygenase branch for alternative (IL-4) anti-inflammatory adaptations. Treatment with IL-4, but not IL-10, primes the ability of astrocytes to activate the innate immunity signaling pathways in response to LPS. Endotoxin-treated astrocytes provide an alternative anti-inflammatory adaptation, which makes cells less sensitive to acute LPS stimulation than the IL-4 induced adaptation. Taken together, the data reveal that oxylipin profiles associate with different states of polarization to generate a pro-inflammatory or anti-inflammatory phenotype. This association manifests itself both in native cells and in their responses to a pro-inflammatory stimulus.

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The efficacy of vitamin B6 as an adjunctive therapy to lithium in improving the symptoms of acute mania in patients with bipolar disorder, type 1; a double‐blind, randomized, placebo‐controlled, clinical trial

et al. 2021

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Objective: Vitamin B6 has been linked to a variety of probable roles, including antiinflammatory, homocysteine-lowering, serotonin-regulating, and dopamine-lowering.In this study, we investigated the possible effect of vitamin B6 on bipolar disorder in manic episode with psychotic feature in a placebo-controlled double-blind clinical trial in a psychiatric hospital. Methods:This study was performed on 50 patients who were equally divided into two groups (each group included 25 patients) using 80 mg of vitamin B6 daily or placebo.At the beginning and end of the study, they were evaluated for lab tests, inflammatory biomarkers and level of blood homocysteine. Also, at the baseline and in weeks 2, 4, and 8, they were evaluated based on the anthropometric measurements, score obtained from the Young Mania Questionnaire, Mini-Mental State Examination (MMSE), and the Pittsburgh Sleep Questionnaire.Results: Accordingly, based on Yang Mania scoring scale, no significant difference was observed between the two groups receiving vitamin B6 and placebo (22.68 ± 5.39 vs. 21.80 ± 5.39 [p-value = .51]). Based on MMSE, significant improvement in cognitive status was obtained in group placebo compared to vitamin B6 group (25.24 ± 1.96 vs. 24.40 ± 3.25, respectively [p-value = .01]). At the Pittsburg scale (total, there was no statistically significant difference between the two groups receiving vitamin B6 and placebo (1.04 ± 0.20 vs. 0.48 ± 0.50 [p-value = .23]). Additionally, no significant difference was observed between the two groups regarding the anthropometric status.Conclusions: According to this study, the daily dose of 80 mg of vitamin B6 for 8 weeks in patients with bipolar disorder in the manic episode with psychotic feature treated daily with lithium, was not associated with a significant improvement in mood status compared to the control-placebo group. It is recommended to perform similar studies in a multi-center manner with a larger sample size and longer duration.

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Resolution of inflammation and mood disorders

Cited by 34 publications

References 202 publications

Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

The efficacy of vitamin B6 as an adjunctive therapy to lithium in improving the symptoms of acute mania in patients with bipolar disorder, type 1; a double‐blind, randomized, placebo‐controlled, clinical trial

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