Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice☆
Section snippets
Animals
All animal procedures complied with the Canadian Council for Animal Care and were approved by the Queen's University Animal Care Committee. CD-1 mice (Charles River Canada Inc., St. Constant, Quebec) weighing 24–28 g were kept in a temperature-controlled room with a 12-h light–dark cycle automatically maintained. Food (Purina Rodent Chow, Ren's Feed and Supply, Oakville, Ontario) and tap water were provided ad libitum. One male mouse was housed with three females overnight between 4:30 pm and
VPA-induced neural tube defects in CD-1 mice
A dose–response profile of VPA-induced exencephaly was created by exposing time-controlled pregnant CD-1 mice to 0, 300, 400, and 600 mg/kg of VPA on GD 9 prior to the period of neural tube closure in these embryos. The neural tube closure status of these mice was evaluated 36 h later, on GD 10.5. VPA (300, 400, and 600 mg/kg) caused a 14 ± 7%, 24 ± 10%, and 40 ± 18.5% incidence of exencephaly, respectively, as compared to control animals (0%), indicating that VPA exposure on GD 9 induces NTDs
Discussion
In previous studies, Padmanabhan and Shafiullah (2003), using the same FA dosing regime used in this study, demonstrated a decrease in VPA-induced NTDs from 38% to 18% in the TO mouse model. Likewise, Sato et al. (1995), using the same PTA dosing regime used in our study, showed a decrease in VPA-induced NTDs from 13.7% to 3.8% in ICR mice. Consistent with these previous studies, in our studies, we found that FA and PTA decreased VPA-induced NTDs from 23.6% to 3.0% and 6.8%, respectively.
The
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Characterizing the effects of in utero valproic acid exposure on NF-κB signaling in CD-1 mouse embryos during neural tube closure
2021, Neurotoxicology and TeratologyCitation Excerpt :In order to be activated NF-κB undergoes a variety of posttranslational modifications including phosphorylation of p65 by Pim-1 at Ser276 which stabilizes p65 (Nihira et al., 2010). As our laboratory reported reduced levels of phosphorylated p65 at Ser276 following VPA exposure in P19 cells (Lamparter et al., 2017) and a significant downregulation in Pim-1 protein levels in VPA-exposed GD10 mouse embryos (Dawson et al., 2006), we examined Pim-1 gene expression in this study. The observed VPA-induced decreases in transcript levels of Pim-1 (Fig. 3a), could be responsible for the depleted levels of phosphorylated/active p65 in VPA-exposed mouse embryos.
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2019, Medical HypothesesCitation Excerpt :Therefore, it is is possible that sildenafil rescues VPA induced teratogenesis both by attenuating peroxynitrite induced inhibition of the NMDA receptor and also by attenuating peroxynitrite induced apoptosis in macrophages. Given that nitric oxide teratogenicity for the neural tube is rescued by folic acid, it may come as no surprise that, in mice, VPA induced teratogenicity to the neural tube is also rescuable by folic acid [54,55]. To demonstrate that M2-like macrophages play a role in influencing neural tube closure on a structural level, one would need to demonstrate that M2-like macrophages are capable of exerting effects, either directly or indirectly, on factors which contribute to the structural integrity of the developing embryo.
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These studies were supported by a grant from the Canadian Institutes of Health Research (to L.M.W. FRN57920) and from the J.P. Bickell Foundation. A preliminary report of this research was presented at the 43rd annual meeting of the Society of Toxicology (U.S.A.) Toxicol. Sci. Suppl. No. 182.