Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions

Daniel J. Curtis, Aman Sood, Tom J. Phillips, Akihiro Nishiguchi, Veron H.L. Leinster, Christopher Coyle, Lizeth Lacharme-Lora, Oliver Beaumont, Helena Kemp, Roberta Goodall, Leila Cornes, Michele Giugliano, Rocco A. Barone, Michiya Matsusaki, Mitsuru Akashi, Hiroyoshi Y. Tanaka, Mitsunobu Kano, Jennifer McGarvey, Nagaraj D. Halemani, Katja SimonRobert Keehan, William Ind, Tracey Masters, Simon Grant, Sharan Athwal, Gavin Collett, Dionne Tannetta, Ian L. Sargent, Emma Scull-Brown, Xun Liu, Kristian Aquilina, Nicki Cohen, Jon D. Lane, Marianne Thoresen, Jon Hanley, Andrew Randall, C. Patrick Case

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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 [Ca2+]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.

Original languageEnglish
Pages (from-to)386-395
Number of pages10
JournalExperimental Neurology
Publication statusPublished - Nov 1 2014
Externally publishedYes


  • Cerebral cortex
  • Dendrite
  • Development
  • Hypoxia
  • Neurodevelopmental disorder
  • Neurone
  • Parvalbumin
  • Placenta
  • Reoxygenation
  • Schizophrenia

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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