Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

Yuki Aoyama, Kazuya Toriumi, Akihiro Mouri, Tomoya Hattori, Eriko Ueda, Akane Shimato, Nami Sakakibara, Yuka Soh, Takayoshi Mamiya, Taku Nagai, Hyoung Chun Kim, Masayuki Hiramatsu, Toshitaka Nabeshima, Kiyofumi Yamada

研究成果: Article

19 引用 (Scopus)

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Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that PNE disrupted the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and subventricular zones. In addition, using a cumulative 5-bromo-2′-deoxyuridine labeling assay, we evaluated the rate of cell cycle progression causing the impairment of neuronal progenitor proliferation, and uncovered anomalous cell cycle kinetics in mice with PNE. Accordingly, the density of glutamatergic neurons in the medial prefrontal cortex (medial PFC) was reduced, implying glutamatergic dysregulation. Mice with PNE exhibited behavioral impairments in attentional function and behavioral flexibility in adulthood, and the deficits were ameliorated by microinjection of D-cycloserine into the PFC. Collectively, our findings suggest that PNE affects the proliferation and maturation of progenitor cells to glutamatergic neuron during neurodevelopment in the medial PFC, which may be associated with cognitive deficits in the offspring.

元の言語English
ページ(範囲)578-589
ページ数12
ジャーナルNeuropsychopharmacology
41
発行部数2
DOI
出版物ステータスPublished - 01-01-2016
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

これを引用

Aoyama, Y., Toriumi, K., Mouri, A., Hattori, T., Ueda, E., Shimato, A., Sakakibara, N., Soh, Y., Mamiya, T., Nagai, T., Kim, H. C., Hiramatsu, M., Nabeshima, T., & Yamada, K. (2016). Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex. Neuropsychopharmacology, 41(2), 578-589. https://doi.org/10.1038/npp.2015.186