Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

Berry Juliandi, Kentaro Tanemura, Katsuhide Igarashi, Takashi Tominaga, Yusuke Furukawa, Maky Otsuka, Noriko Moriyama, Daigo Ikegami, Masahiko Abematsu, Tsukasa Sanosaka, Keita Tsujimura, Minoru Narita, Jun Kanno, Kinichi Nakashima

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31 Citations (Scopus)

Abstract

Prenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running.

Original languageEnglish
Pages (from-to)996-1009
Number of pages14
JournalStem cell reports
Volume5
Issue number6
DOIs
Publication statusPublished - 2015 Dec 8

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Juliandi, B., Tanemura, K., Igarashi, K., Tominaga, T., Furukawa, Y., Otsuka, M., Moriyama, N., Ikegami, D., Abematsu, M., Sanosaka, T., Tsujimura, K., Narita, M., Kanno, J., & Nakashima, K. (2015). Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid. Stem cell reports, 5(6), 996-1009. https://doi.org/10.1016/j.stemcr.2015.10.012