title: Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid.
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.
authors.affiliation: Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Biology, Bogor Agricultural University (IPB), Bogor 16680, Indonesia.
authors.forename: Berry
authors.initials: B
authors.lastname: Juliandi
authors.affiliation: Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanemura
authors.affiliation: Life Science Tokyo Advanced Research Center, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo 142-8501, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Laboratory of Neural Circuit Systems, Institute of Neuroscience, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa 769-2193, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Furukawa
authors.affiliation: Life Science Tokyo Advanced Research Center, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo 142-8501, Japan.
authors.forename: Maky
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Moriyama
authors.affiliation: Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo 142-8501, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Ikegami
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Abematsu
authors.affiliation: Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sanosaka
authors.affiliation: Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Tsujimura
authors.affiliation: Life Science Tokyo Advanced Research Center, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo 142-8501, Japan; Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo 142-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.affiliation: Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: kin1@scb.med.kyushu-u.ac.jp.
authors.forename: Kinichi
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000002:abnormalities* / Q000187:drug effects* / Q000503:physiopathology; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid