RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during CNS viral infection

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 28, 2024

Summary While recent work has identified roles for immune mediators in the regulation of neural activity, capacity cell intrinsic innate signaling within neurons to influence neurotransmission remains poorly understood. However, existing evidence linking with neuronal function suggests that modulation may serve previously undefined host protection during infection central nervous system. Here, we identify a specialized RIPK3, kinase traditionally associated necroptotic death, preserving survival neurotropic flavivirus through suppression excitatory neurotransmission. We show RIPK3 coordinates transcriptomic changes suppress glutamate signaling, thereby desensitizing excitotoxic death. These effects occur independently traditional functions promoting necroptosis and inflammatory transcription. Instead, promotes phosphorylation key regulatory CaMKII, which turn activates transcription factor CREB drive neuroprotective transcriptional program deleterious glutamatergic signaling. findings an unexpected canonical death protein viral highlighting new mechanisms neuroimmune crosstalk.

Язык: Английский

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Serum Levels of Zinc, Albumin, Interleukin-6 and CRP in Patients with Unipolar and Bipolar Depression: Cross Sectional Study

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(5), С. 4533 - 4550

Опубликована: Май 9, 2024

Unipolar (UD) and bipolar depression (BDD) show a high degree of similarity in clinical presentations, which complicates the differential diagnosis these disorders. The aim this study was to investigate serum levels interleukin 6 (IL-6), C-reactive protein (CRP), albumin (Alb), zinc (Zn) patients with UD, BDD, healthy controls (HC). A total 211 samples were collected: 131 patient (65 UD 68 BDD) 80 HC. Montgomery–Asberg Depression Rating Scale (MADRS), along Hamilton (HAMD-17), administered groups evaluate symptoms. cross-sectional performed analyse IL-6, CRP, albumin, zinc. concentration CRP determined using immunoturbidimetry method, colorimetric method bromocresol green on Alinity c device. IL-6 cytokine ascertained commercial enzyme immunoassay, ELISA. We found no significant differences concentrations zinc, between unipolar depression. There statistical difference (p < 0.001) all investigated parameters both depressed comparison Furthermore, correlations specific items HAMD-17; (namely, hypochondrias, work activities, somatic symptoms-general, weight loss) MADRS (concentration difficulties, lassitude) observed groups. These findings confirm presence low-grade inflammation depression, thus adding better insight into hypothesis directed explain aetiology depressive Our results do not indicate potential biomarkers for distinguishing

Язык: Английский

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Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12634 - 12634

Опубликована: Авг. 10, 2023

Over the past few decades, extensive research has shed light on immune alterations and significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to integrity both brain intestinal barriers, may play a crucial role origin peripheral central inflammation these pathologies. Sphingosine-1-phosphate (S1P) is bioactive lipid that regulates response permeability barriers. Notably, S1P-based drugs, such as fingolimod ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease nervous system (CNS), ulcerative colitis, inflammatory condition colon, respectively. Although precise mechanisms action are still under investigation, effectiveness drugs pathologies sparks debate extending their use psychiatry. This comprehensive review aims delve into molecular through which S1P modulates brain/intestinal barrier functions. Furthermore, it will specifically focus diseases, with primary objective uncovering potential innovative therapies based signaling.

Язык: Английский

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Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms

Journal of Personalized Medicine, Год журнала: 2023, Номер 13(12), С. 1689 - 1689

Опубликована: Дек. 5, 2023

Mental disorders that are comorbid with chronic infectious diseases may worsen clinical outcomes and patients' quality of life. We hypothesized depression and/or anxiety syndromes or symptoms human immunodeficiency virus (HIV) hepatitis B (HBV) infection might stem from shared biological mechanisms. conducted a systematic review applying the PRISMA statement by searching into PubMed, APA PsycInfo, Scopus databases. examined literature on HIV/HBV in adults ≥18 years. Thirty-one studies HIV three HBV were analyzed. The Tat protein contributed to HIV-associated mood due protein's ability cause neurodegeneration induce hypothalamic-pituitary-adrenal (HPA) axis dysregulation response natural stressors. decreased brain-derived neurotrophic factor (BDNF) levels also emerged as mechanism involved neuropathogenesis associated symptoms. Neuroinflammation was implicated onset patients infections. Microglial activation release cytokines, particular, appeared potential pathogenetic Furthermore, an altered balance between quinolinic acid kynurenic production depression, indicating glutamatergic dysfunction. Inflammatory cytokine downregulation cellular immune responses persisting inflammation, delayed healing, functional decline (CHB) infection. A shift type 1-type 2 be HBV-related pathogenesis, considered immunomodulatory factors. Cytokines caused HPA hyperactivity, frequently observed depression/anxiety. present showed, for first time, have several mechanisms common denominators. longitudinal course highlighted should explored establish causative interrelationship among In addition, future research investigate possibility patient's outcome improve using pharmacological treatments acting we described denominators inflammatory infective

Язык: Английский

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A blood-free modeling approach for the quantification of the blood-to-brain tracer exchange in TSPO PET imaging

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Июль 22, 2024

Recent evidence suggests the blood-to-brain influx rate (K1 ) in TSPO PET imaging as a promising biomarker of blood-brain barrier (BBB) permeability alterations commonly associated with peripheral inflammation and heightened immune activity brain. However, standard compartmental modeling quantification is limited by requirement invasive laborious procedures for extracting an arterial blood input function. In this study, we validate simplified blood-free methodologic framework K1 estimation fitting early phase tracer dynamics using single irreversible compartment model image-derived function (1T1K-IDIF). The method tested on multi-site dataset containing 177 studies from two tracers ([11C]PBR28 [18F]DPA714). Firstly, 1T1K-IDIF estimates were compared terms both bias correlation kinetic methodology. Then, was independent sample [11C]PBR28 scans before after inflammatory interferon-α challenge, test-retest [18F]DPA714 scans. Comparison methodology showed good-to-excellent intra-subject regional 1T1K-IDIF-K1 (ρintra = 0.93 ± 0.08), although variable depending IDIF ability to approximate functions (0.03-0.39 mL/cm3/min). unveiled significant reduction BBB replicating results quantification. High (ρ 0.97 0.01) reported between test retest This supports alternative assess tracers' unidirectional brain clearance. investigation could complement more traditional measures studies, even allow further mechanistic insight interpretation signal.

Язык: Английский

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