title: Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions.
abstract: Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during foetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and foetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytotrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca(2+)]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers invitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions.
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Curtis
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Aman
authors.initials: A
authors.lastname: Sood
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Phillips
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Veronica H L
authors.initials: VH
authors.lastname: Leinster
authors.affiliation: Department of Applied Chemistry, Osaka University, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishiguchi
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coyle
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Lizeth
authors.initials: L
authors.lastname: Lacharme-Lora
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Beaumont
authors.affiliation: Newborn Screening, Southmead Hospital, Bristol, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Kemp
authors.affiliation: Newborn Screening, Southmead Hospital, Bristol, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Goodall
authors.affiliation: Newborn Screening, Southmead Hospital, Bristol, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Cornes
authors.affiliation: Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Michele
authors.initials: M
authors.lastname: Giugliano
authors.affiliation: Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Rocco A
authors.initials: RA
authors.lastname: Barone
authors.affiliation: Department of Applied Chemistry, Osaka University, Japan.
authors.forename: Michiya
authors.initials: M
authors.lastname: Matsusaki
authors.affiliation: Department of Applied Chemistry, Osaka University, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.affiliation: Department of Molecular Pathology, University of Tokyo, Japan.
authors.forename: Hiroyoshi Y
authors.initials: HY
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Pathology, University of Tokyo, Japan.
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Kano
authors.affiliation: School of Biochemistry, University of Bristol, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McGarvey
authors.affiliation: School of Biochemistry, University of Bristol, UK.
authors.forename: Nagaraj D
authors.initials: ND
authors.lastname: Halemani
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Katja
authors.initials: K
authors.lastname: Simon
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Keehan
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: William
authors.initials: W
authors.lastname: Ind
authors.affiliation: Dept. Obstetrics and Gynaecology, Southmead Hospital, Bristol, UK.
authors.forename: Tracey
authors.initials: T
authors.lastname: Masters
authors.affiliation: Dept. Obstetrics and Gynaecology, Southmead Hospital, Bristol, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Grant
authors.affiliation: Dept. Obstetrics and Gynaecology, Southmead Hospital, Bristol, UK.
authors.forename: Sharan
authors.initials: S
authors.lastname: Athwal
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Collett
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
authors.forename: Dionne
authors.initials: D
authors.lastname: Tannetta
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Sargent
authors.affiliation: Department of Neonatology, University of Bristol, Bristol, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Scull-Brown
authors.affiliation: Department of Neonatology, University of Bristol, Bristol, UK.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Frenchay Hospital, Bristol, UK.
authors.forename: Kristian
authors.initials: K
authors.lastname: Aquilina
authors.affiliation: Department of Neuropathology, University of Bristol, Bristol, UK.
authors.forename: Nicki
authors.initials: N
authors.lastname: Cohen
authors.affiliation: School of Biochemistry, University of Bristol, UK.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Lane
authors.affiliation: Department of Neonatology, University of Bristol, Bristol, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
authors.affiliation: School of Biochemistry, University of Bristol, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Hanley
authors.affiliation: School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Randall
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Bristol University, Southmead Hospital, Bristol BS10 5NB, UK. Electronic address: c.p.case@bristol.ac.uk.
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Case
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000009:adverse effects* / Q000737:chemistry; D003712:Dendrites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D010920:Placenta / Q000737:chemistry* / Q000166:cytology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D017382:Reactive Oxygen Species; D010100:Oxygen
keywords: Cerebral cortex; Dendrite; Development; Hypoxia; Neurodevelopmental disorder; Neurone; Parvalbumin; Placenta; Reoxygenation; Schizophrenia