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Gene expression changes in the developing neural tube from valproic acid and maternal immune stimulation treatments
Author(s) -
Hrubec Terry C,
Li Wen,
Yan Mingjin,
Ye Keying,
Holladay Steven D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a226-c
Subject(s) - valproic acid , neural tube , stimulation , immune system , gene , gene expression , neuroscience , epilepsy , pharmacology , immunology , chemistry , biology , microbiology and biotechnology , genetics , embryo
Valproic acid, a drug commonly used to treat seizures and psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development results in exencephaly and spina bifida. In mice, non specific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including valproic acid (VA) induced NTDs (from 18% to 3%). We hypothesized that VA would alter gene expression regulating growth factors, apoptosis, and closure of the neural tube; and that maternal immune stimulation by IFNγ injection would normalize gene expression in the fetus. CD‐1 mice were given IFNγ or saline pre‐breeding. Half of the control and IFNγ treated females were injected with 500 mg/kg VA on gestational day 8:0. Fetal heads were collected at day 8:15, 9:00 and 9:15; RNA was isolated and quantified by real‐time PCR. Changes in gene expression for TGFα, TGFβ 1, TGFβ2, TGFβ3, Folbp1, Folbp2, rnrR1, p53, Bcl2α, and Bcl2β were analyzed using a linear mixed model with respect to individual genes. There were significant effects of gestational day, drug treatment, and open or closed neural tube; and significant interaction between these effects. Gene expression was also correlated within each age/treatment group indicating significant gene‐gene interaction. Supported by NIH grant K01RR16241‐01