title: The suppression of maternal-fetal leukemia inhibitory factor signal relay pathway by maternal immune activation impairs brain development in mice.
abstract: Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)-placental ACTH-fetal LIF signaling relay pathway (maternal-fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal-fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal-fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis.
authors.affiliation: Department of Neurosurgery, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsukada
authors.affiliation: Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Simamura
authors.affiliation: Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Arai
authors.affiliation: Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Higashi
authors.affiliation: Department of Neurosurgery, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Akai
authors.affiliation: Department of Neurosurgery, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hatta
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005786:Gene Expression Regulation; D007109:Immunity; D015850:Interleukin-6 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130; D000324:Adrenocorticotropic Hormone; D053612:Janus Kinases