التفاصيل البيبلوغرافية
| العنوان: |
Neurodevelopmental signatures of narcotic and neuropsychiatric risk factors in 3D human-derived forebrain organoids |
| المؤلفون: |
M Notaras (10067851), A Lodhi (11209038), E Barrio-Alonso (11209041), C Foord (11209044), T Rodrick (11209047), D Jones (7681196), H Fang (66603), David Greening (9478589), D Colak (11209050) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Uncategorized, Neurosciences, Psychiatry, Neurosciences & Neurology, MATERNAL IMMUNE ACTIVATION, CHILDHOOD-ONSET SCHIZOPHRENIA, ORBITOFRONTAL CORTEX NEURONS, TIMING-DEPENDENT PLASTICITY, HUMAN BRAIN-DEVELOPMENT, RHO-GTPASE RAC1, N-ACETYLCYSTEINE, PRENATAL STRESS, MESSENGER-RNA, CEREBRAL ORGANOIDS, narcotic use, neuropsychiatric illness, forebrain organoids, human-derived |
| الوصف: |
It is widely accepted that narcotic use during pregnancy and specific environmental factors (e.g., maternal immune activation and chronic stress) may increase risk of neuropsychiatric illness in offspring. However, little progress has been made in defining human-specific in utero neurodevelopmental pathology due to ethical and technical challenges associated with accessing human prenatal brain tissue. Here we utilized human induced pluripotent stem cells (hiPSCs) to generate reproducible organoids that recapitulate dorsal forebrain development including early corticogenesis. We systemically exposed organoid samples to chemically defined “enviromimetic” compounds to examine the developmental effects of various narcotic and neuropsychiatric-related risk factors within tissue of human origin. In tandem experiments conducted in parallel, we modeled exposure to opiates (μ-opioid agonist endomorphin), cannabinoids (WIN 55,212-2), alcohol (ethanol), smoking (nicotine), chronic stress (human cortisol), and maternal immune activation (human Interleukin-17a; IL17a). Human-derived dorsal forebrain organoids were consequently analyzed via an array of unbiased and high-throughput analytical approaches, including state-of-the-art TMT-16plex liquid chromatography/mass-spectrometry (LC/MS) proteomics, hybrid MS metabolomics, and flow cytometry panels to determine cell-cycle dynamics and rates of cell death. This pipeline subsequently revealed both common and unique proteome, reactome, and metabolome alterations as a consequence of enviromimetic modeling of narcotic use and neuropsychiatric-related risk factors in tissue of human origin. However, of our 6 treatment groups, human-derived organoids treated with the cannabinoid agonist WIN 55,212-2 exhibited the least convergence of all groups. Single-cell analysis revealed that WIN 55,212-2 increased DNA fragmentation, an indicator of apoptosis, in human-derived dorsal forebrain organoids. We subsequently confirmed induction of DNA damage and apoptosis by WIN 55,212-2 within 3D ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/Neurodevelopmental_signatures_of_narcotic_and_neuropsychiatric_risk_factors_in_3D_human-derived_forebrain_organoids/15081549 |
| DOI: |
10.26181/6103aec764169 |
| الاتاحة: |
https://doi.org/10.26181/6103aec764169 |
| Rights: |
CC BY 4.0 |
| رقم الانضمام: |
edsbas.6D9F3E0E |
| قاعدة البيانات: |
BASE |