Pediatric research, 2021-07, Vol.90 (1), p.82-92
2021
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- Autor(en) / Beteiligte
- Titel
- Neural tube defects: role of lithium carbonate exposure in embryonic neural development in a murine model
- Ist Teil von
- Pediatric research, 2021-07, Vol.90 (1), p.82-92
- Ort / Verlag
- New York: Nature Publishing Group US
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Background Lithium carbonate (Li 2 CO 3 ) is widely used in the treatment of clinical-affective psychosis. Exposure to Li 2 CO 3 during pregnancy increases the risk of neural tube defects (NTDs) in offspring, which are severe birth defects of the central nervous system. The mechanism of Li 2 CO 3 -induced NTDs remains unclear. Methods C57BL/6 mice were injected with different doses of Li 2 CO 3 intraperitoneally on gestational day 7.5 (GD7.5), and embryos collected at GD11.5 and GD13.5. The mechanisms of Li 2 CO 3 exposure-induced NTDs were determined utilizing immunohistochemistry, western blotting, EdU imaging, enzymatic method, gas chromatography-mass spectrometry (GC-MS), ELISA and HE staining. Results The NTDs incidence was 33.7% following Li 2 CO 3 exposure. Neuroepithelial cell proliferation and phosphohistone H3 level were significantly increased in NTDs embryos, compared with control group ( P < 0.01), while the expressing levels of p53 and caspase-3 were significantly decreased. IMPase and GSK-3β activity was inhibited in Li 2 CO 3 -treated maternal and embryonic neural tissues ( P < 0.01 and P < 0.05, respectively), along with decreased levels of inositol and metabolites, compared with control groups ( P < 0.01). Conclusions Lithium-induced NTDs model in C57BL/6 mice was established. Enhanced cell proliferation and decreased apoptosis following lithium exposure were closely associated with the impairment of inositol biosynthesis, which may contribute to lithium-induced NTDs. Impact Impairment of inositol biosynthesis has an important role in lithium exposure-induced NTDs in mice model. Lithium-induced NTDs model on C57BL/6 mice was established. Based on this NTDs model, lithium-induced impairment of inositol biosynthesis resulted in the imbalance between cell proliferation and apoptosis, which may contribute to lithium-induced NTDs. Providing evidence to further understand the molecular mechanisms of lithium-induced NTDs and enhancing its primary prevention.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0031-3998eISSN: 1530-0447DOI: 10.1038/s41390-020-01244-1Titel-ID: cdi_proquest_miscellaneous_2459626187
- Format
- –
- Schlagworte
- 5'-Nucleotidase - metabolism, Animals, Apoptosis, Basic Science Article, Biosynthesis, Birth defects, Cell growth, Central Nervous System - drug effects, Central Nervous System - growth & development, Disease Models, Animal, Female, Glycogen Synthase Kinase 3 beta - metabolism, Inositol - metabolism, Lithium, Lithium Carbonate - adverse effects, Maternal Exposure, Medicine, Medicine & Public Health, Mice, Mice, Inbred C57BL, Neural Tube Defects - chemically induced, Pediatric Surgery, Pediatrics, Pregnancy