ArticleCells2023
Identification of YWHAH as a Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure during Early Development.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Longitudinal Peripheral Blood Transcriptomics Reveal Novel Signatures During Cardiac Allograft Rejection.Transplantation direct · 2026Article
- Chronic in utero oxycodone exposure alters placental small EV proteome and fetal cardiomyopathy-linked pathways.Extracellular vesicles and circulating nucleic acids · 2026Article
- YWHAH‑driven autophagy via MAPK/ERK signaling enhances CRC cell migration and invasion.International journal of molecular medicine · 2025Article
- Comprehensive characterization of chronic midazolam exposure on neonates and long-term neurodevelopment.Molecular psychiatry · 2025Article
- Anti-cancer effect of midazolam via downregulating YWHAH in papillary thyroid cancer cells.Discover oncology · 2025Article
- Protocol for the isolation and characterization of porcine brain region-associated extracellular particles.PloS one · 2025Article
- Distinct cortical morphometric inverse divergence changes in Parkinson's disease correlate with transcriptional expression patterns.NeuroImage. Clinical · 2025Article
- Medication Usage Record-Based Predictive Modeling of Neurodevelopmental Abnormality in Infants under One Year: A Prospective Birth Cohort Study.Healthcare (Basel, Switzerland) · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient. BDEVs from the control and MDZ groups were then characterized using a ZetaView nanoparticle tracking analyzer and transmission electron microscopy analysis. Next, using RT-qPCR, we examined the expression of key ESCRT-related genes involved in EV biogenesis. Lastly, using quantitative mass spectrometry-based proteomics, we mined the BDEV protein cargo that revealed key differentially expressed proteins and associated molecular pathways to be altered post long-term MDZ exposure. Our study characterized the proteome in BDEV cargo from long-term MDZ exposure at early development. Importantly, we identified and validated the expression of YWHAH as a potential target for further characterization of its downstream mechanism and a potential biomarker for the early onset of neurodevelopment and neurodegenerative diseases. Overall, the present study demonstrated long-term exposure to MDZ at early development stages could influence BDEV protein cargo, which potentially impact neural functions and behavior at later stages of development.
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Registered trials
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