Anti-Inflammatory Effects of Peripheral Dopamine

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13816 - 13816

Опубликована: Сен. 7, 2023

Dopamine is synthesized in the nervous system where it acts as a neurotransmitter. also number of peripheral organs well several types cells and has organ-specific functions and, demonstrated more recently, involved regulation immune response inflammatory reaction. In particular, renal dopaminergic very important sodium transport blood pressure particularly sensitive to stimuli that cause oxidative stress inflammation. This review focused on how dopamine tissues mechanisms by which its receptors exert their effects response.

Язык: Английский

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Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder

Genes, Год журнала: 2023, Номер 14(7), С. 1460 - 1460

Опубликована: Июль 17, 2023

Immune gene variants are known to be associated with the risk of psychiatric disorders, their clinical manifestations, and response therapy. This narrative review summarizes current literature over past decade on association polymorphic cytokine genes risk, severity, treatment for severe mental disorders such as bipolar disorder, depression, schizophrenia. A search in databases was carried out using keywords related depressive schizophrenia, inflammation, cytokines. Gene lists were extracted from publications identify common pathways these disorders. Associations between IL1B, IL6, TNFA most replicated relevant depression. Polymorphic IL6R, IL10, IL17A, have been Bipolar disorder has mainly IL1B gene. Interestingly, IL6R polymorphism (rs2228145) all three diseases. Some also presentation pharmacotherapy. There is evidence that some specific may affect expression genes. Thus, data this indicate a link neuroinflammation

Язык: Английский

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Comparative Analysis of Serum BAFF and IL-17 Levels Pre- and Post-Antipsychotic Treatment for Acute Schizophrenia

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 385 - 385

Опубликована: Янв. 4, 2025

The interplay between the cytokine network and antipsychotic treatment in schizophrenia remains poorly understood. This study aimed to investigate impact of psychotropic medications on serum levels IFN-γ, IL-4, TGF-β1, IL-17, BAFF, explore their relationship with psychopathological features. We recruited 63 patients diagnosed acute phase, all whom were either drug-naïve or had been drug-free for at least three months. Serum BAFF measured baseline after six months treatment. severity symptoms was assessed using Brief Psychiatric Rating Scale (BPRS), Assessment Positive Symptoms (SAPS), Negative (SANS). Fifty-two completed six-month follow-up immunoassay analysis. Antipsychotic led a significant decrease alongside increase levels. Changes IFN-γ positively correlated SANS scores negatively Global Functioning (GAF) scores. TGF-β1 GAF SAPS Multivariable regression models used association level changes (IL-17, TGF-β1) independent variables, including demographic (gender, age), behavioral (tobacco use), clinical (schizophrenia type, disease course, date onset, prior treatment), biological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) factors, as well standardized assessment No associations found, except negative correlation scores, positive age. Interestingly, advanced statistical analyses revealed that only IL-17 significantly associated Our findings suggest drugs exert both pro- anti-inflammatory effects network. observed modulation highlights potential future therapeutic targets schizophrenia.

Язык: Английский

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Sex differences in the peripheral levels of cytokines during 12-month antipsychotic treatment in a drug-naïve schizophrenia spectrum cohort

Brain Behavior & Immunity - Health, Год журнала: 2025, Номер 44, С. 100959 - 100959

Опубликована: Фев. 4, 2025

There are substantial sex differences in schizophrenia. However, research addressing regarding the antipsychotic effect on immune system is lacking. The aim of our study was to compare changes cytokine levels men and women with schizophrenia spectrum disorder over 12 months treatment antipsychotics. This reports pre-planned secondary outcomes from BeSt InTro Study - a pragmatic, semi-randomised, rater-blinded comparison amisulpride, aripiprazole, olanzapine. groups were analysed collectively. Of 144 enrolled patients disorders ongoing psychosis, 56 antipsychotic-naïve at baseline (20 36 men) included this study. Blood samples these drawn baseline, prior antipsychotics, 1, 3, 6, 12, 26, 39, 52 weeks after initiation medication. Duration weeks. Serum assessed multiplex immunoassay. Changes IL-4, IL-6, TNF-α, IL-1β, IL-2, IL-10, IL-12p70, IL-17A, IFN-γ CRP different follow-up times using linear mixed effects models separately for women, then compared. Cytokine mainly stable during period. In IL-4 lower compared (p = 0.048) showed consistent significant increase 6 0.006), 26 < 0.001), 39 0.002), 0.001). TNF-α increased 0.008) 0.012). IL-6 had transient 0.003) 0.007). progression 3 (IL-6: p 0.046), (IL-4: 0.022, IL-6: 0.015), 0.01), 0.001, 0.015, TNF-α: 0.026), 0.003, 0.023) 0.009). did not differ between sexes or period change significantly antipsychotics either sex. We found serum drug-naïve altered levels. may dramatically affect mental as well somatic health. Our findings add already established pathophysiology might have potential role future guidelines. Research Council Norway, Western Norway Regional Health Trust, participating hospitals universities provided funding

Язык: Английский

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NGF-β and BDNF levels are altered in male patients with chronic schizophrenia: effects on clinical symptoms

BMC Psychiatry, Год журнала: 2025, Номер 25(1)

Опубликована: Март 13, 2025

Abstract Background Schizophrenia, a severe mental disorder with complex pathophysiology, involves neurotrophic factors, which play crucial roles in neurodevelopment and neuroplasticity. This study investigated NGF-β BDNF levels chronic schizophrenia their association clinical symptoms, cognitive function, 1,25(OH)₂D levels. Methods In this cross-sectional study, 72 male patients 70 matched healthy controls were enrolled. Psychopathological symptoms assessed using the Positive Negative Syndrome Scale (PANSS), function was evaluated Repeatable Battery for Assessment of Neuropsychological Status (RBANS). The serum NGF-β, BDNF, measured. Results Serum (F = 35.239, P < 0.001) 12.669, significantly decreased compared to controls. negatively correlated PANSS negative (beta -0.205, t -2.098, 0.040) positively ( r 0.324, 0.006). Decreased concentrations language deficits -0.301, -2.762, 0.007). Significant associations observed between reduced (B 1.040, 0.001, RR 2.829, 95% CI: 2.101−3.811) 0.526, 1.692, 1.241−2.306). Conclusions Our findings indicated that altered associated vitamin D metabolism. These results provided new insight into etiology schizophrenia.

Язык: Английский

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Biomarkers of endogenous mental disorders: the role of cortisol, extracellular DNA, BDNF, and cytokines in relation to disease stage and therapy

Vestnik nevrologii psihiatrii i nejrohirurgii (Bulletin of Neurology Psychiatry and Neurosurgery), Год журнала: 2025, Номер 2, С. 245 - 258

Опубликована: Фев. 15, 2025

Background. With the growing number of publications on search for biological markers mental disorders, it is important to analyze studies role extracellular DNA, cortisol, cytokines, and BDNF as severity endogenous depending disease stage antipsychotic treatment. Purpose: available data relationship between biomarkers disorders (cortisol, BDNF) stage, well therapy. Materials method. Publications accessible authors were selected from MEDLINE/PubMed, Scopus, Crossref, eLibrary, RSCI databases using key words “biomarkers disorders”, “stress cortisol”, “cytokines “BDNF”, “extracellular DNA”. A total 428 sources identified, 71 selected, primarily 2020 2024, focusing impact marker levels progression their changes under Priority was given meta-analyses systematic reviews, which reflect recent discoveries can significantly influence future research directions. Conclusion. The review analyzes in patients with associations stress, autoimmune disturbances, (first episode, long-term course, relapse, or remission), therapy, biomarker clinical manifestations illness. Correlations identified specific cognitive impairments, positive symptoms, negative symptoms. Research aims enable early diagnosis, develop new therapeutic targets, stratify optimal protocols, providing opportunities address clinical, diagnostic, therapeutic, rehabilitative challenges.

Язык: Английский

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Dopamine-driven increase in IL-1β in myeloid cells is mediated by differential dopamine receptor expression and exacerbated by HIV

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Март 23, 2025

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that regulates critical in peripheral organs an important immunoregulatory factor. We have previously shown increases NF-κB activity, inflammasome activation, the production inflammatory cytokines IL-1β human macrophages. As myeloid lineage cells are to initiation resolution acute responses, dopamine-mediated dysregulation these could both impair innate immune response exacerbate chronic inflammation. However, exact pathways by which drives inflammation not well defined, studies rodent systems indicate can impact mediators through D1-like receptors (DRD1, DRD5) D2-like (DRD2, DRD3, DRD4). Therefore, we hypothesized regulated ratio different activated. Our data primary monocyte-derived macrophages (hMDM) DRD1 expression necessary IL-1β, changes DRD2 other alter magnitude increase IL-1β. Mature hMDM a high receptor ratio, relative monocytes blood mononuclear (PBMCs). further confirm microglia cell lines promotes dopamine-induced gene protein using pharmacological inhibition or overexpression receptors. RNA-sequencing dopamine-treated shows genes encoding signaling pathways, neurotransmission increased with treatment. Finally, HIV example disease substantively worsened comorbid substance use disorders (SUDs) dopaminergic signaling, show effects on activation presence microglia. These suggest addictive substances dopamine-modulating therapeutics dysregulate neuroimmunological conditions like HIV. Thus, detailed understanding inflammation, particular regulating will be effectively tailor medication regimens.

Язык: Английский

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Identification of biomarkers related to propionate metabolism in schizophrenia

Frontiers in Psychiatry, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

Schizophrenia (SCZ) is a severe mental disorder with complex etiology. Research shows propionate metabolism crucial for neurological function and health. This suggests abnormalities in may link to SCZ. Therefore, identifying biomarkers associated might be beneficial the diagnosis treatment of SCZ patients. datasets metabolism-related genes (PMRGs) from public databases were obtained. DE-PMRGs identified through differential correlation analysis PMRGs. Machine learning was used screen key validate expression levels, aiming identify potential biomarkers. Gene Set Enrichment Analysis (GSEA) immune infiltration performed on An upstream regulatory network constructed, drugs targeting these explored. Finally, real-time fluorescence quantitative PCR (qPCR) verify biomarker levels. A total 11 identified, machine technology employed further 5 genes. Among these, LY96 TMEM123 emerged as verification. diagnostic model developed, achieving an area under curve (AUC) greater than 0.7, which indicates strong performance. Additionally, nomograms based demonstrated promising predictive capabilities assessing risk To explore gene functions mechanisms at deeper level, competitive endogenous RNA (ceRNA) including 2 biomarkers, 72 microRNAs, 202 long non-coding RNAs. In addition, containing 104 transcription factors (TFs) also established investigate interacting Potential biomarker-targeted by exploring DrugBank database; notably, exhibited higher binding affinities four drugs, docking scores consistently below-5 kcal/mol. The qPCR results indicated that levels whole blood patients significantly those healthy control group, consistent GSE38484 GSE27383 datasets. study disease SCZ, specifically TMEM123. These findings offer novel perspectives management

Язык: Английский

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B Cell-activating factor (BAFF): A promising trans-nosographic biomarker of inflammation and autoimmunity in bipolar disorder and schizophrenia

Brain Behavior and Immunity, Год журнала: 2024, Номер 121, С. 178 - 188

Опубликована: Июль 22, 2024

Immune dysregulation is an important aspect of schizophrenia (SZ) and bipolar disorders (BD) pathophysiology, including not only inflammatory but also autoimmune process reflective abnormal humoral immune responses. Given that B cell-activating factor (BAFF) integral lymphocyte regulation, the current study investigated BAFF in SZ BD. 255 patients, 407 BD patients 185 healthy controls (HC) were across three aspects soluble (sBAFF) by (i) comparing sBAFF circulatory levels SZ, HC, (ii) determining potential correlations between circulating genotype distribution a functionally relevant polymorphism, namely TNFSF13B 3′UTR insertion-deletion polymorphism (GCTGT>A), (iii) analyzing relationships both genotypes disease risk, clinical characteristics potent molecules. In addition, subsets we searched for possible stigma past infectious events as well positivity systemic autoantibodies or those directed against central nervous system (CNS) structures. Studying blood derived serum DNA, observed significantly higher versus HC (p = 5.3*10-10 p 4.4*10-09). Patients experiencing acute episodes, stable exhibited 0.017). positive elevated and: psychotic symptoms (PANSS pos), history childhood trauma (physical abuse), low scores on global functioning (GAF) 0.024, 0.041). We found Ins/Del was correlated with 0.0004). Elevated increased pro-inflammatory markers cohorts < 0.001). Regarding stigma, seropositive, seronegative, herpes simplex virus (HSV)1 immunoglobulin (Ig)G antibodies significant association high 0.013). contrast, CNS associated reduced levels, compared to without 0.0017). Overall, our findings indicate may be promising trans-nosographic biomarker inflammation likely offer predictive, diagnostic, prognostic tools management The results therefore have practicable utility given availability immunotherapeutic treatment options targeted monoclonal BAFF.

Язык: Английский

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GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia

Molecular Neurobiology, Год журнала: 2024, Номер 61(9), С. 6968 - 6983

Опубликована: Фев. 16, 2024

Abstract The pathogenesis of schizophrenia begins in early neurodevelopment and leads to excitatory-inhibitory imbalance. It is therefore essential that preclinical models used understand disease, select drug targets evaluate novel therapeutics encompass similar neurochemical deficits. One approach improved modelling incorporates dual-hit neurodevelopmental insults, like neonatal administration phencyclidine (PCP, disrupt development glutamatergic circuitry) then post-weaning isolation (Iso, mimic adolescent social stress). We recently showed male Lister-hooded rats exposed PCP-Iso exhibit reduced hippocampal expression the GABA interneuron marker calbindin. current study expanded on this by investigating changes additional populations GABAergic interneurons frontal cortical tissue from same animals (by immunohistochemistry) as well levels itself (via ELISA). Because inflammatory are also implicated schizophrenia, we performed immunohistochemical evaluations Iba-1 positive microglia ELISA analysis IL-6 brain regions. Single-hit isolation-reared both parvalbumin immunoreactivity prelimbic/infralimbic region cortex. However, was more widespread PCP-Iso, extending medial/ventral lateral/dorsolateral orbitofrontal cortices. Loss markers accompanied increased microglial activation cortices together with elevations not seen following single-hit rearing. These findings enhance face validity advocate use model for future evaluation therapeutics—especially those designed normalise imbalance or reduce neuroinflammation.

Язык: Английский

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