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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)578-589
Number of pages12
JournalNeuropsychopharmacology
Volume41
Issue number2
DOIs
Publication statusPublished - 01-01-2016

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Prefrontal Cortex
Nicotine
Neurons
Cell Cycle
Cycloserine
Pregnancy
Lateral Ventricles
Learning Disorders
Microinjections
Bromodeoxyuridine
Attention Deficit Disorder with Hyperactivity
Stem Cells
Anxiety
Smoking

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Aoyama, Yuki ; Toriumi, Kazuya ; Mouri, Akihiro ; Hattori, Tomoya ; Ueda, Eriko ; Shimato, Akane ; Sakakibara, Nami ; Soh, Yuka ; Mamiya, Takayoshi ; Nagai, Taku ; Kim, Hyoung Chun ; Hiramatsu, Masayuki ; Nabeshima, Toshitaka ; Yamada, Kiyofumi. / Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex. In: Neuropsychopharmacology. 2016 ; Vol. 41, No. 2. pp. 578-589.
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abstract = "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.",
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Aoyama, Y, Toriumi, K, Mouri, A, Hattori, T, Ueda, E, Shimato, A, Sakakibara, N, Soh, Y, Mamiya, T, Nagai, T, Kim, HC, 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, vol. 41, no. 2, pp. 578-589. https://doi.org/10.1038/npp.2015.186

Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex. / Aoyama, Yuki; Toriumi, Kazuya; Mouri, Akihiro; Hattori, Tomoya; Ueda, Eriko; Shimato, Akane; Sakakibara, Nami; Soh, Yuka; Mamiya, Takayoshi; Nagai, Taku; Kim, Hyoung Chun; Hiramatsu, Masayuki; Nabeshima, Toshitaka; Yamada, Kiyofumi.

In: Neuropsychopharmacology, Vol. 41, No. 2, 01.01.2016, p. 578-589.

Research output: Contribution to journalArticle

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AU - Mouri, Akihiro

AU - Hattori, Tomoya

AU - Ueda, Eriko

AU - Shimato, Akane

AU - Sakakibara, Nami

AU - Soh, Yuka

AU - Mamiya, Takayoshi

AU - Nagai, Taku

AU - Kim, Hyoung Chun

AU - Hiramatsu, Masayuki

AU - Nabeshima, Toshitaka

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