SARS-CoV2 vaccination during pregnancy – Vetting the impact on maternal health and long-term consequences for offspring brain function

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

Published: April 1, 2025

The COVID-19 pandemic has shown the critical importance of vaccination strategies to protect vulnerable populations, including pregnant women, from severe disease and its lingering consequences. Although growing evidence demonstrates that vaccines are both safe highly beneficial during pregnancy, vaccine hesitancy among women persists, partly fueled by persistent, decade-old "urban myth" linking pregnancy neuropsychiatric disorders in children. Here, we used a mouse model passive immunization with acute respiratory syndrome coronavirus 2 spike neutralizing monoclonal antibodies (SaCoV-AB) determine effects gestational on key outcomes, maternal offspring health, behavior. We show at higher SaCoV-AB dosage, immune response is reflected elevated TNF-α levels serum, but not placenta or fetal brain, no effect outcomes. report consequences for postpartum care behavior neonatal communication signatures. Behavioral assessment adult female male after treatment revealed differences phenotypes relevant neurodevelopmental disorders. Our findings indicate preclinical model, well-tolerated, discernable impact health

Language: Английский

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Maternal noninfectious fever during pregnancy modulates offspring social behaviour in rats: An exploratory study

International Journal of Obstetric Anesthesia, Journal Year: 2025, Volume and Issue: unknown, P. 104374 - 104374

Published: April 1, 2025

Language: Английский

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Exploring the link between grandmaternal air pollution exposure and Grandchild’s ASD risk: A multigenerational population-based study in California

Environment International, Journal Year: 2025, Volume and Issue: unknown, P. 109526 - 109526

Published: May 1, 2025

Language: Английский

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Pregestational Prediabetes Induces Maternal Hypothalamic–Pituitary–Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5431 - 5431

Published: May 16, 2024

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading adverse outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated effects maternal on HPA axis function postnatal offspring development. Hence, this study pregestational Pre-diabetic (PD) non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from PD NPD groups collected. Markers function, adrenocorticotropin hormone (ACTH) corticosterone, measured all dams pups. Glucose tolerance, insulin gene expressions mineralocorticoid (MR) glucocorticoid (GR) receptors further at birth their developmental milestones. The results demonstrated increased basal concentrations ACTH corticosterone group comparison NPD. Furthermore, show an increase concentrations, disturbed MR GR expression, glucose intolerance resistance assessed via Homeostasis Model Assessment (HOMA) indices compared These observations reveal that associated dysregulation impacting development along impaired handling.

Language: Английский

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Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Fetal Outcomes: Influences on HPA Axis and Development

Published: March 29, 2024

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading adverse outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated effects maternal on HPA axis function postnatal offspring development, hence this study. Pre-diabetic (PD) non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from PD NPD groups collected. Markers function, adrenocorticotropin hormone (ACTH) corticosterone measured all dams pups. Glucose tolerance expression mineralocorticoid (MR) glucocorticoid (GR) receptors further at birth their developmental milestones. The results demonstrated increased basal concentrations ACTH group comparison NPD. Furthermore, show an increase concentrations, impaired glucose dysregulated MR GR These observations reveal that pregestational associated dysregulation impacting development along handling.

Language: Английский

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A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)‐ Associated Hypothalamic‐Pituitary‐Adrenal (HPA) Axis Dysregulation: Exploring Links to Pregestational Prediabetes

Published: April 16, 2024

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for Developmental Origins Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which fetus is highly susceptible to specific environmental influences significantly impact health from short long term. Maternal stress T2DM pregnancy are among these influences, likely leading overexposure glucocorticoids suggesting shared pathway between maternal dysregulated HPA axis insults. Studies demonstrate prenatal glucocorticoid exposure alters function, affecting brain tissue availability, growth in utero. These programmed changes, such as altered function reduced growth, contribute metabolic disorders persisting into adulthood. preceded by prediabetic state, often asymptomatic, shares similar pathophysiological complications T2DM, including dysregulation observed animals. Therefore, investigating prediabetes alongside its effects on outcomes crucial, areas remain understudied. review aims synthesize existing literature pre-existing pregnancy, links programming via possible pregestational prediabetes.

Language: Английский

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A bibliometric analysis of autism spectrum disorder signaling pathways research in the past decade

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 12, 2024

Background This study employs bibliometric methods to comprehensively understand the fundamental structure of research about Autism Spectrum Disorder (ASD) Signaling Pathways by examining key indicators such as nations, institutions, journals, authors, and keywords. Methodology We utilized WoScc database retrieve literature relevant ASD published between 2013 2023. Through visual analysis tools like CiteSpace VosViewer, we explored keywords, thereby constructing networks. Results 26 The encompasses 1,396 articles, revealing a consistent increase in publications. United States, China, Germany are leading nations this literature. Regarding University California system Eric Klann have garnered significant attention due their substantial contributions field Pathways. Most is journal “Molecular Autism.” Research interests concentrated across various themes, including “elevating neuronal β-catenin levels,” “Tunisian children,” “ Fmr1 knockout (KO) mice,” de novo mutations,” “autistic “local translation,” “propionic acid-induced mouse models,” “neurosystems,” “glucose metabolism,” “neuronal migration.” Future may emphasize exploring aspects gut microbiota, genes, stress, maternal immune activation, memory, neurodevelopmental disorders ASD. Conclusion study, through provides comprehensive overview current state on These investigations predominantly focus molecular mechanisms, animal model studies, population-based research, function neurosystems. directions also clearly proposed. First, in-depth genes associated with will continue reveal genetic basis provide support for precise treatments. At same time, microbiota help explore its association ASD, which clues new In addition, relationship stress become better emotional behavioral characteristics patients stressful situations. Maternal activation be further studied how environmental factors influence risk development Finally, deeper understanding cognitive functions especially memory learning, develop individualized treatment strategies improve patients’ quality life. work together expected more ideas opportunities future intervention treatment.

Language: Английский

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Translational study on the role of genetic and prenatal risk factors in neurodevelopmental psychiatric disorders

Published: Jan. 1, 2024

Neurodevelopmental psychiatric disorders (NPDs) like attention deficit hyperactivity disorder (ADHD), autism spectrum (ASD), and schizophrenia, affect millions of people worldwide. Despite recent progress in NPD research, much remains to be discovered about their underpinnings, therapeutic targets, effects biological sex age. Risk factors influencing brain development signalling include prenatal inflammation genetic variation. This dissertation aimed build upon these findings by combining behavioural, molecular, neuromorphological investigations mouse models such risk factors, i.e. maternal immune activation (MIA), neuron-specific overexpression (OE) the cytoplasmatic isoforms RNA-binding protein RBFOX1, neuronal deletion small Ras GTPase DIRAS2. Maternal infections during pregnancy pose an increased for NPDs offspring. While viral-like MIA has been previously established elsewhere, this study was first our institution implement model. I validated NPD-relevant deficits anxiety- depression-like behaviours, as well dose- sex-specific social offspring following early gestation. Proteomic analyses embryonic adult hippocampal (HPC) synaptoneurosomes highlighted novel known targets affected MIA. Analysis dataset implicated neurodevelopmental disruptions lipid, polysaccharide, glycoprotein metabolism, important proper membrane function, signalling, myelination, NPD-pertinent sequelae. In adulthood, observed changes encompassed transmembrane trafficking intracellular apoptosis, cytoskeletal organisation pathways. Importantly, 50 proteins altered HPC were enriched synaptic vesicle cycle. A persistently upregulated cluster formed a functional network involved presynaptic downregulated embryos but adults correlated with deficits. 49/50 genes encoding significantly associated NPD- comorbidity-relevant traits human phenome-wise association data phenotypes. These highlight future intervention at-risk individuals. MIA-evoked neuroarchitecture prefrontal cortex (PFC) male female mice sex- region-specific alterations dendritic spine morphology, possibly underlining behavioural To further investigate NPDs, performed based on implications RBFOX1’s pleiotropic role neuropsychiatric previous preclinical findings. Cytoplasmatic OE which affects stability translation thousands used disseminate its morphology behaviour. RBFOX1 length branching PFC led both HPC. Due ASD-like endophenotypes Rbfox1 KO importance gene × environment susceptibility, probed interaction low-dose Both alone loss perinatal period. Preliminary suggested that might increase anhedonia-like behaviours. Morphological density reduced complexity. post-mortem dorsolateral older did not reveal significant common variant abundance. expand risks, evaluated homo- (KO) or heterozygous (HET) Diras2 novel, DIRAS2’s function is largely unknown, it ADHD humans neurodevelopment vitro. mice, there subtle behaviour, more pronounced males, keeping data. had subtly improved cognitive performance, while HET exhibited behaviours line core symptoms, e.g. earning difficulties (females), response inhibition (males), suggesting dose-sensitivity sex-specificity. The morphological revealed multiple aberrations PFC, HPC, amygdala males. KOs exclusively opposite those HETs NPD-like Region- genotype-specific expression Diras1 six relevant regions females, also revealing differences survival regulator mTOR, underlie differences. conclusion, partial knockdown resembled each other core, NPD-associated phenotypes, full differed from those. My suggest complex sex-dependent relationships between interventions, whose influences converge onto molecular An assessment putative overlap, available proteomic three linked via downstream interactions, upstream regulators. Future studies should distinct shared aspects MIA, DIRAS2

Language: Английский

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A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1372 - 1372

Published: June 20, 2024

Research has identified fetal risk factors for adult diseases, forming the basis Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural functional changes in organs, increasing chronic diseases like type 2 diabetes mellitus (T2DM) adulthood. It is proposed altered physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis stress T2DM pregnancy, exposes fetus to excess GC. Prenatal exposure reduces growth programs HPA axis, permanently altering its activity into This programmed linked risks hypertension, cardiovascular mental disorders With global rise T2DM, particularly among young adults reproductive age, it crucial prevent onset. often preceded by prediabetic state, condition does not show any symptoms, causing many unknowingly progress T2DM. Studying prediabetes essential, reversible stage may help T2DM-related complications. The existing literature focuses on dysregulation pregnancies link programming. However, effects function, specifically outcomes, are well understood. review consolidates research impact programming via possible links pregestational prediabetes.

Language: Английский

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Maternal Immune Activation and Autism Spectrum Disorder: Complex Interactions and Therapeutic Possibilities

International journal for autism challenges & solution., Journal Year: 2024, Volume and Issue: 1(1), P. 39 - 50

Published: April 19, 2024

This review examines the intricate association between maternal immune activation (MIA) and autism spectrum disorder (ASD), emphasizing impact of infections during pregnancy. Epidemiological studies link viral bacterial to an elevated risk ASD, revealing complex interplay environmental factors neurodevelopmental outcomes. Immunological mechanisms, including cytokine dysregulation neuroinflammation, involve key players such as interleukin-6 tumor necrosis factor-alpha, influencing fetal brain development ASD risk. Genetic interactions contribute individual susceptibility, with specific variants MIA's on Epigenetic modifications provide a molecular exposures, MIA, enduring changes. Recognizing critical periods neurodevelopment susceptible MIA is crucial. Long-term highlight consequences behavior cognition into childhood adolescence. Exploring potential therapeutic interventions, immunomodulatory strategies pregnancy, offers hope for mitigating Despite progress, knowledge gaps persist, motivating future research guided by emerging technologies interdisciplinary approaches unravel MIA-ASD relationship.

Language: Английский

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