Differential effects of purified low molecular weight Poly(I:C) in the maternal immune activation model depend on the laboratory environment DOI Creative Commons
Katharina Tillmann,

Ron Schaer,

Flavia S. Mueller

et al.

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 20, 2024

The Poly (I:C) (polyriboinosinic-polyribocytidilic acid) paradigm of maternal immune activation (MIA) is most widely used as experimental model for the evaluation effects gestational infection on brain and behavior progeny. We have previously reported significant batch-to-batch variability in (I:C), purchased from same supplier (Sigma-Aldrich), fetal responses found these differences to be dependent relative amount synthetic double-stranded RNA fragments high versus low molecular weight (LMW) range contained compound. here resorted purified LMW dsRNA establish a MIA with increased reproducibility enhanced standardization an effort refine characterize its effect offspring behavior. that parallel application two different MIA-experienced laboratories (Vienna Zurich) yielded differential outcomes terms behavioral phenotypes generation. In both sites, administration induced sickness response cytokine induction pregnant dam brains, while expected deficit sociability one main outcome parameter progeny, was only present Zurich, but not Vienna cohort. conclude although using defined reduces variability, it does make more reliable robust. between illustrates highly complex interaction prenatal postnatal milieus - including laboratory environment determine phenotypic after MIA. Consequently, establishing new protocol or implementing firstly under changed environmental conditions must include assessment ensure solid reproducible outcomes.

Language: Английский

Repeated LPS induces training and tolerance of microglial responses across brain regions DOI Creative Commons
Jennifer Kim,

Olivia Sullivan,

Kristen M. Lee

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Sept. 20, 2024

Neuroinflammation is involved in the pathogenesis of almost every central nervous system disorder. As brain's innate immune cells, microglia fine tune their activity to a dynamic brain environment. Previous studies have shown that repeated bouts peripheral inflammation can trigger long-term changes microglial gene expression and function, form memory.

Language: Английский

Citations

6
Regional skull translocator protein elevation in autistic adults detected by PET-MRI DOI Creative Commons
Chieh-En Jane Tseng, Elisa Guma, Christopher J. McDougle

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Maternal peptidoglycan overexposure during late pregnancy alters neurodevelopment and behavior in juvenile offspring DOI
Inés Martínez Sánchez,

Julia Spielbauer,

Rochellys Diaz Heijtz

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Brain-derived exosome biomarkers of neuroinflammation and neuronal functional iron deficiency in newborns of overweight-obese mothers DOI

Phu V. Tran,

Andrew C. Harris,

Zia L. Maxim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Maternal adiposity induces inflammation that may cause fetal neuroinflammation and brain iron deficiency, thus neurodevelopmental risk. Currently, there is a lack of brain-specific biomarkers identify neonates who are at risk, limiting the ability to screen intervene early in life, when interventions have greatest impact on neurodevelopment. Leveraging emerging technology purifies nanoparticles secreted from into circulation, this study assessed feasibility quantifying inflammatory markers carried within these index status using small volume cord blood. Newborns overweight-obese mothers exhibit evidence low-level peripheral pro-inflammation with normal systemic status. In contrast, shows anti-inflammatory responses functional deficiency demonstrating not accurately reflect processes. The discovery quantifiable brain-derived blood samples serves as proof-of-concept infants at-risk for long-term adverse health outcomes could be identified by non-invasive assays before becoming apparent later life. Graphical

Language: Английский

Citations

0
Exogenous PD-L1 binds to PD-1 to alleviate and prevent autism-like behaviors in maternal immune activation-induced male offspring mice DOI
Xin Zeng,

Linlin Fan,

Qian Qin

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 122, P. 527 - 546

Published: Aug. 24, 2024

Language: Английский

Citations

1
Deciphering the Role of Maternal Microchimerism in Offspring Autoimmunity: A Narrative Review DOI Creative Commons
Alexandra Mpakosi, Rozeta Sokou,

Martha Theodoraki

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(9), P. 1457 - 1457

Published: Sept. 5, 2024

Feto-maternal microchimerism is the bidirectional transfer of cells through placenta during pregnancy that can affect health both mother and offspring, even in childhood or adulthood. However, seems to have different consequences mother, who already has a developed immune system, than fetus, which vulnerable with immature defense mechanisms. Studies shown presence fetal microchimeric be associated reduced growth, pre-eclampsia, miscarriage, premature birth, risk autoimmune disease development future. some studies report they may also play positive role healing maternal tissue, cancer cardiovascular disease. There are few literature regarding autoimmunity. Even fewer examined their association potential triggering diseases later offspring's life. The objectives this review were elucidate mechanisms underlying between conditions offspring. Based on our findings, several hypotheses been proposed possible by trigger In Type 1 diabetes, implicated either attacking pancreatic β-cells, producing insulin, differentiating into endocrine exocrine cells, serving as markers tissue damage. Additionally, suggested for onset neonatal lupus erythematosus. context, induce graft-versus-host host-versus-graft reaction function effectors within tissues, contribute healing. These found participate inflammation fibrosis processes, well differentiate myocardial potentially an response. Moreover, involvement supported such juvenile idiopathic inflammatory myopathies, Sjögren's syndrome, systemic sclerosis, biliary atresia, rheumatoid arthritis. Conversely, no celiac findings suggest autoimmunity remains controversial topic warrants further investigation.

Language: Английский

Citations

1
Dysregulation of the mTOR-FMRP pathway and synaptic plasticity in an environmental model of ASD DOI Creative Commons

Muna L. Hilal,

Eleonora Rosina, G Pedini

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Abstract Autism Spectrum Disorder (ASD) is caused by genetic, epigenetic, and environmental factors. Mutations in the human FMR1 gene, encoding Fragile X Messenger Ribonucleoprotein 1 (FMRP), cause most common monogenic form of ASD, Syndrome (FXS). This study explored interaction between gene a viral-like infection as an insult, focusing on impact core autistic-like behaviors mGluR1/5-mTOR pathway. Pregnant heterozygous Fmr1 mouse females were exposed to maternal immune activation (MIA), injecting immunostimulant Poly (I:C) at embryonic stage 12.5, simulating viral infections. Subsequently, ASD-like analyzed adult offspring, 8–10 weeks age. MIA exposure wild-type mice led offspring. These effects specifically confined intrauterine infection, later stages, namely puberty (Pubertal Immune Activation, PIA) post-natal day 35 or adulthood (Adult AIA) 56, did not alter behavior. Importantly, combining mutation with intensify behaviors, suggesting occlusion effect. Mechanistically, provided strong pathway, leading increased LTP downregulation FMRP hippocampus. Finally, modulates mTOR activity via TSC2. findings further strengthen key role pathway causing symptoms.

Language: Английский

Citations

1
Sex-dependent cytokine release; KATNAL2 gene; auditory processing in fragile X syndrome DOI

Jill Adams

The Transmitter, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection DOI Creative Commons
Samantha Ottinger, Allison R. Larson, Vicki Mercado-Evans

et al.

Published: Oct. 25, 2024

ABSTRACT Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated are not well-described. We established a murine maternal UTI model which challenge with uropathogenic E. coli resulted about half dams. Dams experiencing displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, no differences bacterial burdens. Additional factors associated included higher proportions male fetuses lower serum IL-10. Furthermore, exogenous IL-10 treatment absolved but contributed fetal growth restriction this model. Using urine samples from cohort human pregnancies or without UTI, we correlated cytokines outcomes culture status. These analyses yielded non-invasive, highly predictive three-model system evaluating implicating IL-10, IL-15, IL-1β, IL-1RA. Our unique bimodal coupled patient provides platform investigate immunological microbial governing birth, revealing novel therapeutic opportunities predict prevent birth.

Language: Английский

Citations

0
IL-17A Alters Human Cortical Development in a 3D Ex Vivo Model of Maternal Immune Activation DOI Creative Commons
Muhammad Zaman Khan Assir,

Mario Yanakiev,

Do Hyeon Gim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Abstract Human brain development depends on the coordinated interaction of diverse cell types and extracellular matrix (ECM) components, which are essential for proper neurogenesis cortical organization. Epidemiological animal studies have demonstrated that maternal immune activation (MIA) disrupts development, leading to impaired increased risk neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) schizophrenia. However, cellular molecular mechanisms by MIA impacts human remain poorly understood. Here we introduce a 3D ex vivo culture system, termed ‘cerebroids,’ derived from dorsolateral prefrontal cortex fetal tissue, faithfully preserves key developmental processes, along with critical diversity structural integrity developing cortex. Using this platform, show IL-17A, cytokine strongly implicated in NDDs, induces premature folding, increases thickness, accelerates neuronal maturation. Transcriptomic proteomic analyses reveal significant dysregulation ECM-related pathways, upregulation proteoglycans such as brevican versican. Notably, treatment anti-inflammatory agent parthenolide, an inhibitor NF-κB HDAC1 reverses IL-17A-induced abnormalities, restoring normal neurogenesis. These findings provide valuable insights into how IL-17A during MIA, advancing our understanding NDD-associated alterations.

Language: Английский

Citations

0