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Louise Winn's lab identify neural tube defects with in utero exposure to an epilepsy drug in mice

Research Showcase - Louise Winn

Highlights

•Gestational valproic acid exposure perturbates NF-kB signaling in a mouse model.

Valproic acid exposure downregulates p65, Pim-1, p105/p50 mRNA in GD9 mouse embryos.

•Downregulated p50 protein levels are observed in valproic acid induced exencephaly.

This paper is the third in a series of studies carried out by my PhD student Sidra Shafique evaluating whether the therapeutic drug valproic acid interferes with normal embryonic signalling. Recently, the use of this well-known antiepileptic drug for the treatment of psychiatric conditions has been on the rise. However, it is also well-known that exposure to valproic acid during pregnancy can affect embryonic development, including being associated with neural tube defects. Here we present results that gestational valproic acid exposure in mice leads to downregulated gene expression of NF-kB signaling pathway molecules including p65, p105/p50, Pim-1 and p50 protein expression, which we propose may play a role in valproic acid-initiated teratogenesis. Even in light of its teratogenic profile, valproic acid continues to be prescribed to women of childbearing age. While prescriptions to treat epilepsy are on the decline, it is increasingly prescribed to treat psychiatric conditions such as bipolar disorder and schizophrenia in women of childbearing age. As a result, a complete understanding of the mechanism of teratogenicity and its downstream effects is imperative.

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