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

Exp Neurol. 2014 Nov;261:386-95. doi: 10.1016/j.expneurol.2014.05.003. Epub 2014 May 10.

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.

Keywords: Cerebral cortex; Dendrite; Development; Hypoxia; Neurodevelopmental disorder; Neurone; Parvalbumin; Placenta; Reoxygenation; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain* / cytology
  • Brain* / growth & development
  • Brain* / pathology
  • Cell Hypoxia / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Culture Media, Conditioned / adverse effects*
  • Culture Media, Conditioned / chemistry
  • Dendrites / drug effects
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Female
  • Fetus
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Hypoxia* / drug therapy
  • Hypoxia* / pathology
  • Hypoxia* / physiopathology
  • Membrane Potentials / drug effects
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / physiology
  • Oxygen / pharmacology*
  • Placenta / chemistry*
  • Placenta / cytology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Tissue Culture Techniques

Substances

  • Culture Media, Conditioned
  • Glial Fibrillary Acidic Protein
  • Reactive Oxygen Species
  • Oxygen