Effects of minocycline and rapamycin in gamma-irradiated human embryonic stem cells-derived cerebral organoids

Radiation induces DNA and protein damage and free radical formation, effectively establishing cellular senescence in a variety of models. We demonstrate the effects of two known pleiotropic drugs following gamma radiation damage in neurosphere/cerebral organoid system based on human embryonic stem c...

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Bibliographic Details
Published in:Molecular biology reports 2019-02, Vol.46 (1), p.1343-1348
Main Authors: Shakhbazau, Antos, Danilkovich, Natalya, Seviaryn, Ihar, Ermilova, Tatyana, Kosmacheva, Svetlana
Format: Article
Language:English
Subjects:
Acidification
Animal Anatomy
Animal Biochemistry
Antibiotics
Biomedical and Life Sciences
Deoxyribonucleic acid
DNA
DNA damage
Embryo cells
Embryos
Histology
Life Sciences
Metabolic activation
Metabolic rate
Metabolism
Minocycline
Morphology
Organoids
Rapamycin
Senescence
Short Communication
Stem cells
Ventricle
Ventricles (cerebral)
γ Radiation
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Summary:Radiation induces DNA and protein damage and free radical formation, effectively establishing cellular senescence in a variety of models. We demonstrate the effects of two known pleiotropic drugs following gamma radiation damage in neurosphere/cerebral organoid system based on human embryonic stem cells. mTORC1 repression by rapamycin prior to irradiation, or metabolic activation by minocycline after irradiation, partially rescues neuroepithelium integrity, neurite-growing capacity, ventricle formation and extracellular acidification rate as an integral measure of metabolic output. Cerebral organoid model thus provides valid and robust readouts for radiation studies in a complex 3D setting.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-018-4552-6