Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long‐Term Functional Evaluation

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

ABSTRACT Human midbrain organoids with functional dopaminergic (DA) neurons are invaluable for the therapeutic development of Parkinson's disease (PD). However, current methods face significant limitations, including challenges in generating pint‐sized enriched DA and lack robust assays efficiently evaluating neural networks over extended periods. Here we present an innovative approach that combines developmental patterning mechanical cutting to produce small organoids, diameters less than 300 μm, suitable long‐term evaluation, along a comprehensive assay system consisting calcium transient assay, neurite extension multielectrode array (MEA) assay. Radial into four eight portions according their sizes at appropriate stage significantly increases yield viable while reducing necrotic cell regions. Using system, demonstrate within extend long projections, respond dopamine stimulation, form characterised by giant depolarising potential‐like events. Our supports generation PD models can be used testing.

Language: Английский

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Animal models of post-acute COVID-19 syndrome: a call for longitudinal animal studies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

Animal models are indispensable for unraveling the mechanisms underlying post-acute sequelae of COVID-19 (PASC). This review evaluates recent research on PASC-related perturbations in animal models, drawing comparisons with clinical findings. Despite limited number studies post-COVID conditions, particularly those extending beyond three months, these provide valuable insights. Three hallmark features PASC-lung fibrosis, hyperglycemia, and neurological sequelae-have been successfully replicated paving way mechanistic discoveries future medical interventions. Although most have reported conditions within 14-60 days post-infection, they still offer critical reference long-term research. also explores potential persisting immune misfiring, a key factor chronicity PASC symptoms. Moreover, challenges modeling discussed, including genetic diversity inbred strains difficulties accurately identifying PASC-affected individuals. To address issues, we propose methodological improvements, such as comparing individual parameters control averages incorporating genetically diverse populations like collaborative cross models. These strategies will enhance identification characterization endotypes studies. By integrating findings from manifestations PASC, can more insights into its support development effective therapeutic strategies. Finally, emphasize urgent need longitudinal to fully uncover driving guide interventions mitigate public health impact.

Language: Английский

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A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 604 - 604

Published: March 1, 2025

Background/Objectives: Parkinson’s disease (PD) is a neuro-degenerative for which radical cure not available, only symptomatic control. Studies have shown that hypoxia may disease-modifying effects on PD. Methods: Herein, we investigated whether short-term activates astrocytes and it has protective effect pre-formed fibril (PFF)-treated primary cortical neurons. Results: Long-term suppresses astrocyte activation induces cell death, whereas without affecting cellular apoptosis or viability. Short-term restored the viability of PFF-treated neurons reduced toxic phospho-α-synuclein (p-α-syn) aggregation. Similarly, hypoxia-exposed astrocyte-conditioned medium rescued p-α-syn expression. Quantitative polymerase chain reaction revealed promotes A2 A1 astrocytes. Conclusions: Our findings suggest neuro-protective against PD by activating astrocytes, rescue PFF-induced neuronal death. This provides insights into clinical implications as strategy.

Language: Английский

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Adhesive and Conductive Fibrous Hydrogel Bandages for Effective Peripheral Nerve Regeneration

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Abstract Peripheral nerve injury is a common disease resulting in reversible and irreversible impairments of motor sensory functions. In addition to conventional surgical interventions such as grafting neurorrhaphy, guidance conduits are used effectively support axonal growth without unexpected neuroma formation. However, there still challenges secure tissue‐mimetic mechanical electrophysiological properties the conduit materials. Herein, phenylborate‐tethered hydrogel‐assisted doping effect elucidated on conductive polymers, enhancing peripheral regeneration when sutureless bandage injured nerve. The adhesive consists biocompatible hyaluronic acid hydrogel microfibers produced by electrospinning, followed situ polypyrrole polymerization fibrous mat. Particularly, phenylborate groups enable high adsorption pyrrole crack network allow tissue‐like stretchability on‐nerve adhesiveness. rat crushed model, can promote through stable wrapping great electrical transmission defect region, showing anatomical functional recovery tissues preventing muscular atrophy. Such bandages will be promising dressing combined with versatile biomedical devices/materials for repair.

Language: Английский

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Animal Models for Long COVID: Current Advances, Limitations, and Future Directions

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Long COVID (LC) represents a chronic, systemic, and often disabling condition that poses significant ongoing threat to public health. Foundational scientific studies are needed unravel the underlying mechanisms, with ultimate goal of developing effective preventative therapeutic strategies. Therefore, there is an urgent demand for animal models can accurately replicate clinical features LC. This review integrates epidemiological data summarize pathological changes in extrapulmonary systems involved Additionally, it critically examines capacity existing models, including nonhuman primates, genetically modified mice, Syrian hamsters, exhibit enduring postinfection symptoms align human manifestations, identifies key areas requiring further development. The objective offer insights will aid development next‐generation thereby accelerating our understanding how acute respiratory viral infections transition into chronic conditions, ensuring preparedness future pandemics.

Language: Английский

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Hamsters with long Covid exhibits a neurodegenerative signature in the brainstem

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

Published: Dec. 16, 2024

Abstract After infection with SARS-CoV-2, patients may present one or more symptoms that appear persist over time, including fatigue, respiratory, cardiovascular and neurological disorders. Neurological include anxiety, depression impaired short-term memory. However, the exact underlying mechanisms of long Covid are not yet decrypted. Using golden hamster as a model, we provide further evidence SARS-CoV-2 is neuroinvasive can in central nervous system, found viral RNA replicative virus brainstem after 80 days infection. Infected hamsters presented neurodegenerative signature brainstem, overexpression innate immunity genes, impacted dopaminergic glutamatergic synapses, altered energy metabolism. Finally, infected manifested persistent signs memory, well late-onset valuable model to study Covid. Conclusively, virus-related immunometabolic coexist contribute manifestation neuropsychiatric cognitive symptoms. Highlights infects persists intranasally-inoculated Persistent consequences observed SARS-CoV-2-infected The distinct transcriptome profiles acute systems affected affects expression genes related processes

Language: Английский

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