Medical Science

Regulation of Neural Stem Cells by a Histone Deacetylases Inhibitor, Valproic Acid
Berry Juliandi, Bogor Agricultural University (IPB)

Histone deacetylases (HDACs) are the chromatin modifiers that can epigenetically regulate neural stem cells (NSCs) fate choice. Activity of HDACs can be altered by chemicals such as valproic acid (VPA), a widely used anticonvulsant and mood stabilizer drug, which recently has been shown to have an HDACs inhibition properties. Although several studies have reported that taking VPA during early pregnancy could lead to developmental abnormalities of the future offspring, it is currently still allowed to be prescribed to pregnant patients if this drug is the only medication that adequately controls seizures.

Here, I demonstrated that transient prenatal exposure of VPA to mouse embryo during prominent neurogenic phase resulted in an enhancement of embryonic cortical neurogenesis. Neurogenesis was promoted using indirect pathway that form the intermediate progenitor cells, which mainly differentiated into Cux1-positive superficial-layer neurons, at the expense of direct pathway that generate Ctip2-positive deep-layer neurons. As a result, cortical laminarization at postnatal was disrupted, with an increase and decrease of superficial-layer (layer II-IV) and deep-layer (layer V-VI) thickness, respectively.

At their adult stages, I found that VPA-treated mice showed poor performance in several learning and memory tasks. Further, I observed that prenatal VPA exposure impaired adult hippocampal NSC proliferation and differentiation, implying that these impairments contribute to those poor performances in learning and memory tasks. Interestingly, voluntary running improved adult hippocampal NSC proliferation and differentiation, and recovered some of the learning and memory deficiencies in VPA-treated mice.

Taken together, these results imply that histone acetylation is an important factor for the NSC differentiation. It also suggests that epigenetic alteration in NSCs at embryonic stage can still persisted until adulthood, affecting learning and memory. Nevertheless, this alteration and its outcomes can be recovered, if not completely, by voluntary running.

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  • Prügivedu

    interesting videos, thanks for sharing all this stuff

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