Modeling cerebral development in vitro with L-MYC-immortalized human neural stem cell-derived organoids

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

Published: Feb. 13, 2025

A promising advance for ex vivo studies of human brain development and formulation therapeutic strategies has been the adoption organoids that, to a greater extent than monolayer or spheroid cultures, recapitulate varying extents patterns tissue cell differentiation brain. Previously, such hampered by limited access relevant tissue, inadequate in vitro models, necessity using rodent models that imperfectly reproduce physiology. Here we present novel organoid-based research platform utilizing L- MYC -immortalized fetal neural stem cells (LMNSC01) grown physiological 4% oxygen environment. We visualized developmental processes LMNSC01 over 120 days immunofluorescence NanoString gene expression profiling. Gene revealed profiling were quantitatively compared those occurring during normal (BrainSpan database) Singscore method. observe similar developing cortex genes characterizing neurons, astrocytes, oligodendrocytes, multiple pathways including involved apoptosis, neuronal cytoskeleton, neurotransmission, metabolism. Notable properties this are its initiation with immortalized authentic cells, growth environment, consistency produced, favorable comparison their reported cortical development. E x advanced recapitulating utero differentiation. here an employing (4% oxygen) Characterizing (using NanoString), then comparing these profiles database), astrocytes oligodendrocytes. NSCs, at concentration, subsequent observed

Language: Английский

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Plexin B2 in physiology and pathophysiology of the central nervous system

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114627 - 114627

Published: April 14, 2025

Language: Английский

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Microglial Colonization Routes and Their Impacts on Cellular Diversity

Neuroscience Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Shedding light on microglial dysregulation in Alzheimer’s disease: exploring molecular mechanisms and therapeutic avenues

Inflammopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Language: Английский

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Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Nov. 20, 2024

Uncontrolled and chronic inflammatory states in the Central Nervous System (CNS) are hallmark of neurodegenerative pathology every injury or stroke-related insult. The key mediators these neuroinflammatory glial cells known as microglia, resident immune cell at core event, astroglia, which encapsulate insults proteoglycan-rich scar tissue. Since majority neuroinflammation is exclusively based on responses said glia, their phenotypes have been identified to be an spectrum encompassing developmental, homeostatic, reparative behaviors opposed ability affect devastating death cascades tissue formation. Recently, research groups focused peptide discovery identify phenotypes, find novel mechanisms, mediate re-engineer actions. Peptides retain diverse function proteins but significantly reduce activity dependence delicate 3D structures. Several peptides targeting unique microglia astroglia identified, along with several capable mediating deleterious promoting beneficial outcomes context neuroinflammation. A comprehensive review will provided primary methodologies, including top-down approaches using biomolecules naïve strategies phage libraries.

Language: Английский

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Maternal Exposure to 4-Tert-Octylphenol Causes Alterations in the Morphology and Function of Microglia in the Offspring Mouse Brain

Published: Jan. 1, 2024

Language: Английский

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Tumor-Associated Macrophages and Their Role in Cancer Progression and Treatment Strategies

Interdisciplinary cancer research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Application of diceCT to Study the Development of the Zika Virus Infected Mouse Brain

Published: July 11, 2024

Zika virus (ZIKV) impacts the developing brain. Here a technique was applied to define, in 3D, developmental changes brain of ZIKV-infected mice. Postnatal day 1 mice were uninfected or ZIKV-infected, then analysed by iodine staining and micro-CT scanning (diffusible contrast enhanced micro-CT; diceCT) at 3-, 6- 10-days post infection (dpi). Multiple regions visualised using diceCT; olfactory bulb, cerebrum, hippocampus, midbrain, interbrain, cerebellum, along with lens retina eye. Brain computationally segmented quantitated, increased volumes time Conversely, mice, no quantitative differences seen 3 6 dpi, when there are clinical signs, but qualitatively, diverse visual defects identified 6-10 dpi. By 10 had significantly lower body weight reduced volume compared dpi-uninfected 6dpi Nissl immunofluorescent Iba1 on post-diceCT tissue successful, RNA extraction not. Thus, diceCT shows utility for detecting both 3D qualitative benefit, post-diceCT, retaining ability apply traditional histology analysis tissue.

Language: Английский

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Microglia: The Drunken Gardeners of Early Adversity

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 964 - 964

Published: Aug. 8, 2024

Early life adversity (ELA) is a heterogeneous group of negative childhood experiences that can lead to abnormal brain development and more severe psychiatric, neurological, medical conditions in adulthood. According the immune hypothesis, ELA leads an response characterized by high levels inflammatory cytokines. This contributes health outcomes refractory treatment individuals with history ELA. Here, we examine this hypothesis context recent rodent studies focus on impact microglia, resident cells brain. We review progress our ability mechanistically link molecular alterations microglial function during critical period changes synaptic connectivity, cognition, stress reactivity later life. also research showing induces long-term "secondary hits" such as traumatic injury, substance use, exposure additional conclude discussion future directions unresolved questions regarding signals modify clinical significance for humans.

Language: Английский

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Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain

Viruses, Journal Year: 2024, Volume and Issue: 16(8), P. 1330 - 1330

Published: Aug. 20, 2024

Zika virus (ZIKV) impacts the developing brain. Here, a technique was applied to define, in 3D, developmental changes brains of ZIKV-infected mice. Postnatal day 1 mice were uninfected or ZIKV-infected, then analysed by iodine staining and micro-CT scanning (diffusible contrast-enhanced micro-CT; diceCT) at 3-, 6-, 10-days post-infection (dpi). Multiple brain regions visualised using diceCT: olfactory bulb, cerebrum, hippocampus, midbrain, interbrain, cerebellum, along with lens retina eye. Brain computationally segmented quantitated, increased volumes time Conversely, mice, no quantitative differences seen 3 6 dpi when there clinical signs, but qualitatively, diverse visual defects identified 6–10 dpi. By 10 dpi, had significantly lower body weight reduced volume compared dpi-uninfected Nissl immunofluorescent Iba1 on post-diceCT tissue successful, RNA extraction not. Thus, diceCT shows utility for detecting both 3D qualitative benefit, post-diceCT, retaining ability apply traditional histology analysis tissue.

Language: Английский

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