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

Lookup NU author(s): Dan Curtis

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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 [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.


Publication metadata

Author(s): Curtis DJ, Sood A, Phillips TJ, Leinster VHL, Nishiguchi A, Coyle C, Lacharme-Lora L, Beaumont O, Kemp H, Goodall R, Cornes L, Giugliano M, Barone RA, Matsusaki M, Akashi M, Tanaka HT, Kano M, McGarvey J, Halemani ND, Simon K, Keehan R, Ind W, Masters T, Grant S, Athwal S, Collett G, Tannetta D, Sargent IL, Scull-Brown E, Liu X, Aquilian K, Cohen N, Lane JD, Thoresen M, Hanley J, Randall A, Case CP

Publication type: Article

Publication status: Published

Journal: Experimental Neurology

Year: 2014

Volume: 261

Pages: 386–395

Print publication date: 01/11/2014

Online publication date: 10/05/2014

Acceptance date: 01/05/2014

ISSN (print): 0014-4886

ISSN (electronic): 1090-2430

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.expneurol.2014.05.003

DOI: 10.1016/j.expneurol.2014.05.003

PubMed id: 24818543


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