title: Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex.
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.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, Japan.|Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Toriumi
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mouri
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Ueda
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Shimato
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Sakakibara
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Soh
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Mamiya
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hiramatsu
authors.affiliation: Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.|Nabeshima Laboratory, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, Japan.|Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018722:Nicotinic Agonists; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009538:Nicotine