title: Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice.
abstract: Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life.
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Pharmacology, Inje Univeirsity College of Medicine, Busan, Republic of Korea.
authors.forename: Sangzin
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kihwan
authors.initials: K
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Brain Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
authors.forename: Usman
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.|Interdisciplinary Program in Brain Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.|Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced* / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012919:Social Behavior; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D014635:Valproic Acid; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse