Regional skull translocator protein elevation in autistic adults detected by PET-MRI

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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

Язык: Английский

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Synergistic impact of early-life stress and prenatal immune activation on spatial memory and oxidative metabolism in rat cortico-limbic networks

Neurobiology of Learning and Memory, Год журнала: 2025, Номер 219, С. 108060 - 108060

Опубликована: Май 1, 2025

Early life exposure to immune activation and stress are critical factors involved in the development of mental neurodevelopmental disorders adulthood. This study explored individual combined effects prenatal lipopolysaccharide-induced (LPS)-induced postnatal maternal separation on cognitive performance oxidative metabolism male Wistar rats. Using a 2 × factorial design, pregnant dams were exposed LPS or saline gestational day 15, offspring underwent from days 2-14. In adulthood, function was assessed using Morris Water Maze, regional brain energy evaluated quantitative histochemistry cytochrome c oxidase (CCO) prefrontal cortex, hippocampus, retrosplenial cortex. Rats both stressors demonstrated significant impairments spatial memory flexibility, supporting "two-hit" hypothesis early adversity, which posits that an adverse environmental event (first hit) with subsequent during developmental periods (second can significantly increase risk developing behavioral Accordingly, adult animals showed prolonged escape latencies decreased retention tasks. Concurrently, CCO activity markedly increased all measured regions, reflecting heightened metabolic demands. These changes consistent impaired hippocampal-prefrontal-retrosplenial network integration underlying key processes alterations such as attention. underscores synergistic these dysfunction, providing translational model better understand etiology disorders. The findings highlight importance addressing multiple interacting context adversity.

Язык: Английский

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IL-17A Alters Human Cortical Development in a 3D Ex Vivo Model of Maternal Immune Activation

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

Опубликована: Окт. 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.

Язык: Английский

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Early environmental influences on brain development and executive function

Brain and Cognition, Год журнала: 2024, Номер unknown, С. 106241 - 106241

Опубликована: Ноя. 1, 2024

Язык: Английский

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Maternal immune activation and neuropsychiatric disease in offspring: Pathogen's perspective

Decoding Infection and Transmission, Год журнала: 2024, Номер 2, С. 100029 - 100029

Опубликована: Янв. 1, 2024

Язык: Английский

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