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Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma.
Nat Cell Biol
January 2025
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM.
View Article and Find Full Text PDFMitotic block and epigenetic repression underlie neurodevelopmental defects and neurobehavioral deficits in congenital heart disease.
Nat Commun
January 2025
Department of Pediatrics and Department of Developmental Biology, University of Pittsburgh, Pittsburgh, USA.
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease associated with microcephaly and poor neurodevelopmental outcomes. Here we show that the Ohia HLHS mouse model, with mutations in Sap130, a chromatin modifier, and Pcdha9, a cell adhesion protein, also exhibits microcephaly associated with mitotic block and increased apoptosis leading to impaired cortical neurogenesis. Transcriptome profiling, DNA methylation, and Sap130 ChIPseq analyses all demonstrate dysregulation of genes associated with autism and cognitive impairment.
View Article and Find Full Text PDFThe Role of Glial Cells in Autism Spectrum Disorder: Molecular Mechanisms and Therapeutic Approaches.
CNS Neurol Disord Drug Targets
January 2025
Department of Pharmacy, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad (UP)-244001, India.
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Emerging evidence highlights the significant role of glial cells, particularly astrocytes and microglia, in the pathophysiology of ASD. Glial cells are crucial for maintaining homeostasis, modulating synaptic function, and responding to neural injury.
View Article and Find Full Text PDFMultigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain.
Toxics
December 2024
Laboratory of Neuropharmacology and Epigenetics, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland.
Benzophenone-3 (BP-3), commonly used as a UV filter in personal care products and as a stabilizer, is an alleged endocrine disruptor with potential neurodevelopmental impacts. Despite its abundance in the environment, the studies on its effect on brain development are scarce, especially in terms of multigenerational impact. In this work, for the first time, we examined neurotoxic and pro-apoptotic effects of BP-3 on mouse brain regions (cerebral cortex and hippocampus) in both the first (F) and second (F) generations after maternal exposure to environmentally relevant BP-3 levels.
View Article and Find Full Text PDFEpigenetic Regulation and Neurodevelopmental Disorders: From MeCP2 to the TCF20/PHF14 Complex.
Genes (Basel)
December 2024
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Background: Neurodevelopmental disorders (NDDs) affect approximately 15% of children and adolescents worldwide. This group of disorders is often polygenic with varying risk factors, with many associated genes converging on shared molecular pathways, including chromatin regulation and transcriptional control. Understanding how NDD-associated chromatin regulators and protein complexes orchestrate these regulatory pathways is crucial for elucidating NDD pathogenesis and developing targeted therapeutic strategies.
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