Aflatoxin B1 Exposure Aggravates Neurobehavioral Deficits and Immune Dysfunctions of Th1, Th9, Th17, Th22, and T Regulatory Cell-Related Transcription Factor Signaling in the BTBR T+Itpr3tf/J Mouse Model of Autism

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(11), P. 1519 - 1519

Published: Oct. 27, 2023

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by impaired communication, reciprocal social interactions, restricted sociability deficits, and stereotyped behavioral patterns. Environmental factors genetic susceptibility have been implicated in an increased risk of ASD. Aflatoxin B1 (AFB1) typical contaminant food feed that causes severe immune dysfunction humans animals. Nevertheless, the impact ASD on immunological responses has not thoroughly examined. To investigate this phenomenon, we subjected BTBR T+Itpr3tf/J (BTBR) mice to AFB1 evaluated their marble-burying self-grooming behaviors sociability. The exposure resulted notable escalation activities while concurrently leading decline contacts. In addition, investigated potential molecular mechanisms underlie production Th1 (IFN-γ, STAT1, T-bet), Th9 (IL-9 IRF4), Th17 (IL-17A, IL-21, RORγT, STAT3), Th22 (IL-22, AhR, TNF-α), T regulatory (Treg) (IL-10, TGF-β1, FoxP3) cells spleen. This was achieved using RT-PCR Western blot analyses assess mRNA protein expression brain tissue. significant upregulation various immune-related factors, including IFN-γ, T-bet, IL-9, IRF4, IL-17A, RORγ, STAT3, IL-22, TNF-α mice. Conversely, IL-10, FoxP3 CD4+ observed be downregulated. Exposure demonstrated rise Th1/Th9/Th22/Th17 levels decrease Treg. results above underscore significance intensifying neurobehavioral abnormalities mice, hence indicating necessity for more comprehensive investigation into contribution development

Language: Английский

---

The Exposure to Lead (Pb) Exacerbates Immunological Abnormalities in BTBR T+ Itpr3tf/J Mice through the Regulation of Signaling Pathways Relevant to T Cells

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16218 - 16218

Published: Nov. 11, 2023

Autism spectrum disorder (ASD) is a common neurodevelopmental illness characterized by abnormal social interactions, communication difficulties, and repetitive limited behaviors or interests. The BTBR T+ Itpr3tf/J (BTBR) mice have been used extensively to research the ASD-like phenotype. Lead (Pb) hazardous chemical linked organ damage in human body. It regarded as one of most metal exposure sources has connected development neurological abnormalities. We flow cytometry investigate molecular mechanism behind effect Pb on subsets CD4+ T cells spleen expressing IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, Foxp3. Furthermore, using RT-PCR, we studied expression numerous genes brain tissue, including increased population CD4+IFN-γ+, CD4+T-bet+, CD4+STAT1+, CD4+STAT4+, CD4+IL-9+, CD4+IRF4+, CD4+IL-22+, CD4+AhR+ mice. In contrast, CD4+IL-10+ CD4+Foxp3+ were downregulated Pb-exposed compared those treated with vehicle. led significant increase AhR mRNA IL-10 Foxp3 was significantly lower Our data suggest that exacerbates immunological dysfunctions associated ASD. These imply may risk

Language: Английский

---

Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-β1/Smad2/3 pathways: the role of Isochlorogenic acid a

Toxicology Research, Journal Year: 2024, Volume and Issue: 13(3)

Published: May 1, 2024

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), phenolic present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity ICR mice. An evaluation performed on oxidative stress, inflammation fibrosis, related signaling. The results indicate that attenuates abnormal liver function. reduced stress caused by Pb. abated fibrosis decreased inflammatory cytokines interleukin-1β (IL-1β) tumor necrosis factor-alpha (TNF-α). abrogated reductions activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Masson staining revealed collagen fiber deposition fibrotic livers. Western blot immunohistochemistry analyses showed increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. also expression I, α-smooth muscle actin (α-SMA), extracellular signal-regulated (p-ERK), c-jun N-terminal (p-JNK), p-p38, signal transducer activator transcription 3 (p-STAT3), transforming growth factor β1 (TGF-β1), p-Smad2/3 livers Overall, ameliorates hepatitis inhibiting AMPK/MAPKs/NF-κB STAT3/TGF-β1/Smad2/3 pathways.

Language: Английский

---

Cadmium exposure exacerbates immunological abnormalities in a BTBR T+ Itpr3tf/J autistic mouse model by upregulating inflammatory mediators in CD45R-expressing cells

Journal of Neuroimmunology, Journal Year: 2023, Volume and Issue: 386, P. 578253 - 578253

Published: Dec. 3, 2023

Language: Английский

---

Lead contamination in human milk affects infants’ language trajectory: results from a prospective cohort study

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Aug. 13, 2024

Infants growing up in low- and middle-income countries are at increased risk of suffering adverse childhood experiences, including exposure to environmental pollution lack cognitive stimulation. In this study, we aimed examine the levels metals human milk women living São Paulo City, Brazil, determine effects on infants’ neurodevelopment. For such, a total 185 samples were analyzed for arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd) using inductively coupled plasma mass spectrometry (ICP-MS). We applied Bayley scales infant toddler development Third Edition (Bayley-III) assess developmental milestones. our analysis, found mean (standard deviation) concentration As equal 2.76 (4.09) μg L −1 , followed by Pb 2.09 (5.36) Hg 1.96 (6.68). Cd was not detected. observed that infants exposed presented language trajectories lower than non-exposed (β = −0.413; 95% CI -0.653, −0.173) after adjustment age, maternal education, socioeconomic status, sex, sample weights. Our results report As, Pb, contamination milk, decreased development. These evidence maternal-child its detrimental impact health.

Language: Английский

---

Novel plasma cytokines identified and validated in children during lead exposure according to the new updated BLRV

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 5, 2024

Lead is a pervasive environmental contaminant with significant health risks, particularly to children. It known for its neurotoxic and immunotoxic effects, causing developmental, cognitive, behavioral impairments. Despite extensive research, the mechanisms of lead toxicity remain unclear. Cytokines, which are critical in immune response inflammation, have emerged as potential biomarkers toxicity. The recent Centers Disease Control Prevention (CDC) update blood reference value (BLRV) 3.5 µg/dL emphasizes need explore novel mechanisms. study involved 100 healthy children aged 1 5 years, divided into two groups based on BLRV: elevated (≥ µg/dL) low (< µg/dL). research consisted phases: discovery validation. Plasma samples were analyzed using RayBio® Human Cytokine Antibody Arrays Enzyme-linked immunosorbent assay (ELISA) cytokine levels. Ethical approval was obtained, statistical analyses included t-tests, chi-squared tests, pearson correlations, multivariate logistic regression. Protein-protein interaction (PPI), Gene Ontology (GO) enrichment, Kyoto Encyclopedia Genes Genomes (KEGG) pathway conducted roles differentially expressed proteins (DEPs). No differences age, gender, or BMI between groups, but BLRV levels significantly higher group compared group. In phase, changes expression identified, including increased IL-6, IL-8, IL-17, decreased BDNF, BMP-4, IGF-1, IL-7, IL-10, Leptin. These findings validated second phase ELISA. Significant positive correlations found IL-17. Negative observed Multivariate regression confirmed that affects these PPI networks revealed DEPs had strong interactions multiple proteins, indicating their central role GO KEGG highlighted pathways related neurotoxicity inflammatory responses, "negative regulation myotube differentiation," "neurotrophin signaling pathway," "alcoholism." This provides insights cytokines offers comprehensive analysis involved. underscore importance early detection intervention updated thresholds.

Language: Английский

---