Microglial priming by IFN‐γ involves STAT1‐mediated activation of the NLRP3 inflammasome DOI Creative Commons

Haili He,

Xiaomei Zhang, Hui He

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)

Published: Oct. 1, 2024

Abstract Background Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial “priming”. Interferon (IFN)‐γ is known cause priming, but mechanism unclear. Methods We examined effects of IFN‐γ on gene expression, activation, inflammatory activity NLRP3 inflammasome primary microglia brains mice. Results Our results showed treating cultures with induced a hedgehog‐like morphology upregulated markers activation (CD86, CD11b) pro‐inflammatory molecules (IL‐1β, IL‐6, TNF‐α, iNOS), while downregulating homeostasis (CX3CR1, CD200R1), anti‐inflammatory (MCR1, Arg‐1) neurotrophic factors (IGF‐1, BDNF). also (NLRP3, caspase‐1, gasdermin D, IL‐18). This particular transcriptional profiling makes IFN‐γ‐primed exaggerated upon lipopolysaccharide (LPS) stimulation. The level NLRP3, IL‐1β, IL‐18, TNF‐α iNOS treated both LPS were highest than either one alone. Injecting into lateral ventricle mice similar morphological functional changes hippocampal cultures. from or hippocampus abolished when STAT1 was inhibited using fludarabin. alone together anxiety‐ depression‐like behaviors impaired hippocampus‐dependent spatial memory; these mitigated by Conclusions primes activating STAT1, which upregulates genes activate inflammasome. Inhibiting IFN‐γ/STAT1 axis be way treat neurodegenerative diseases psychiatric involve priming.

Language: Английский

Preventive Role of Cocoa-Enriched Extract Against Neuroinflammation in Mice DOI Creative Commons
Iván Carrera, Lola Corzo,

Olaia Martínez-Iglesias

et al.

Neurology International, Journal Year: 2025, Volume and Issue: 17(4), P. 47 - 47

Published: March 24, 2025

Background: Chronic aberrant inflammation is a crucial step in mediating cerebrovascular and neurodegenerative pathologies, including Alzheimer’s Parkinson’s disease. Due to their exceptional antioxidant properties ability alter imbalance metabolism reactive response, cocoa-derived flavanols are being investigated as potential bioactive substances modulate reverse these inflammation-associated disorders. Objective: The present study will focus on the possible beneficial effects of extract, enhanced with other phytochemicals such spirulina pineapple, selected biomarkers inflammatory, metabolic, processes. Methods: A mice model was treated extract cocktail, biomolecular data obtained by performing immunohistochemical biochemical analysis. Results: Results show that mitigates neuroinflammatory processes triggered (decreased expression macrophage CD11b) prevents escalade subsequent neurodegeneration pathologies. Conclusions: results based hypo-vitaminosis, neuroinflammation, inmunoreactive analysis suggest powerful bioproduct for ameliorating mediate metabolic diseases.

Language: Английский

Citations

0

Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status DOI Creative Commons
Menglong Geng, Zhen Yu, Yafei Wang

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 30, 2025

Epidemiological studies that have simultaneously explored the effects of placental and cord blood inflammatory cytokine levels on neurodevelopment in offspring, as well role maternal vitamin D these associations, are lacking. To investigate associations with 18-month-old children, potential modification effect by D. Based Ma'anshan birth cohort, current study involved 1241 mother-child pairs. The mRNA expression levels, serum concentrations, concentrations were determined. Children's neurodevelopmental outcomes defined Chinese version Ages Stages Questionnaire (Third Edition) subdomain scores below established cutoff scores. Generalized linear models utilized to assess cytokines examine After adjusting for confounders, each one-unit increase IL-6 (OR = 1.30, 95% CI: 1.09, 1.55, P-FDR 0.024), IL-8 1.25, 1.05, 1.49, 0.036), IFN-γ level 1.74, 1.16, 2.61, 0.042) was associated an increased risk fine motor delay. Elevated TNF-α 1.38, 1.12, 1.69, 0.012), 1.29, 1.04, 1.61, 0.042), 1.31, 1.06, 1.62, 0.036) personal-social Stratified analyses showed lower (< 20 ng/mL) moderated between markers delays motor, gross subdomains. specific placenta umbilical developmental a parental-reported screening tool. Maternal status can modify adverse intrauterine pro-inflammatory milieu children.

Language: Английский

Citations

0

High-throughput CRISPR technology: a novel horizon for solid organ transplantation DOI Creative Commons
Xiaohan Li, Zhang Chen, Weicong Ye

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Organ transplantation is the gold standard therapy for end-stage organ failure. However, shortage of available grafts and long-term graft dysfunction remain primary barriers to transplantation. Exploring approaches solve these issues urgent, CRISPR/Cas9-based transcriptome editing provides one potential solution. Furthermore, combining gene with an ex vivo perfusion system would enable pre-implantation grafts. How determine effective intervention targets becomes a new problem. Fortunately, advent high-throughput CRISPR screening has dramatically accelerated targets. This review summarizes current advancements, utilization, workflow in various immune non-immune cells. It also discusses ongoing applications CRISPR/Cas-based prospective solid

Language: Английский

Citations

3

Differentiation and regulation of CD4+ T cell subsets in Parkinson’s disease DOI Creative Commons
Xiaowei Sun,

Rou Gu,

Jie Bai

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Aug. 17, 2024

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its hallmark pathological features are loss of dopaminergic (DA) neurons in midbrain substantia nigra pars compacta (SNpc) accumulation alpha-synuclein (α-syn). It has been shown that integrity blood-brain barrier (BBB) damaged PD patients, a large number infiltrating T cells inflammatory cytokines have detected cerebrospinal fluid (CSF) brain parenchyma patients animal models, including significant change proportion different CD4

Language: Английский

Citations

3

Microglial priming by IFN‐γ involves STAT1‐mediated activation of the NLRP3 inflammasome DOI Creative Commons

Haili He,

Xiaomei Zhang, Hui He

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)

Published: Oct. 1, 2024

Abstract Background Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial “priming”. Interferon (IFN)‐γ is known cause priming, but mechanism unclear. Methods We examined effects of IFN‐γ on gene expression, activation, inflammatory activity NLRP3 inflammasome primary microglia brains mice. Results Our results showed treating cultures with induced a hedgehog‐like morphology upregulated markers activation (CD86, CD11b) pro‐inflammatory molecules (IL‐1β, IL‐6, TNF‐α, iNOS), while downregulating homeostasis (CX3CR1, CD200R1), anti‐inflammatory (MCR1, Arg‐1) neurotrophic factors (IGF‐1, BDNF). also (NLRP3, caspase‐1, gasdermin D, IL‐18). This particular transcriptional profiling makes IFN‐γ‐primed exaggerated upon lipopolysaccharide (LPS) stimulation. The level NLRP3, IL‐1β, IL‐18, TNF‐α iNOS treated both LPS were highest than either one alone. Injecting into lateral ventricle mice similar morphological functional changes hippocampal cultures. from or hippocampus abolished when STAT1 was inhibited using fludarabin. alone together anxiety‐ depression‐like behaviors impaired hippocampus‐dependent spatial memory; these mitigated by Conclusions primes activating STAT1, which upregulates genes activate inflammasome. Inhibiting IFN‐γ/STAT1 axis be way treat neurodegenerative diseases psychiatric involve priming.

Language: Английский

Citations

3