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

Daniel J. Curtis, Aman Sood, H. L. ica, 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 Tanaka, Mitsunobu Kano, Jennifer McGarvey, Nagaraj D. HalemaniKatja Simon, Robert 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 journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)386-395
Number of pages10
JournalExperimental Neurology
Volume261
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Placenta
Neurons
Brain
Conditioned Culture Medium
Glutamate Receptors
Trophoblasts
Glutamic Acid
Parvalbumins
GABA Receptors
First Pregnancy Trimester
Cerebral Cortex
Free Radicals
Psychiatry
Hypoxia
Young Adult
Hippocampus
Spine
Fetus
Mothers
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Medicine(all)

Cite this

Curtis, D. J., Sood, A., ica, H. L., Phillips, T. J., Nishiguchi, A., Leinster, V. H. L., ... Case, C. P. (2014). Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions. Experimental Neurology, 261, 386-395. https://doi.org/10.1016/j.expneurol.2014.05.003

Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions. / Curtis, Daniel J.; Sood, Aman; ica, H. L.; Phillips, Tom J.; Nishiguchi, Akihiro; Leinster, Veron H L; Coyle, Christopher; Lacharme-Lora, Lizeth; Beaumont, Oliver; Kemp, Helena; Goodall, Roberta; Cornes, Leila; Giugliano, Michele; Barone, Rocco A.; Matsusaki, Michiya; Akashi, Mitsuru; Tanaka, Hiroyoshi; Kano, Mitsunobu; McGarvey, Jennifer; Halemani, Nagaraj D.; Simon, Katja; Keehan, Robert; Ind, William; Masters, Tracey; Grant, Simon; Athwal, Sharan; Collett, Gavin; Tannetta, Dionne; Sargent, Ian L.; Scull-Brown, Emma; Liu, Xun; Aquilina, Kristian; Cohen, Nicki; Lane, Jon D.; Thoresen, Marianne; Hanley, Jon; Randall, Andrew; Case, C. Patrick.

In: Experimental Neurology, Vol. 261, 2014, p. 386-395.

Research output: Contribution to journalArticle

Curtis, DJ, Sood, A, ica, HL, Phillips, TJ, Nishiguchi, A, Leinster, VHL, Coyle, C, Lacharme-Lora, L, Beaumont, O, Kemp, H, Goodall, R, Cornes, L, Giugliano, M, Barone, RA, Matsusaki, M, Akashi, M, Tanaka, H, 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, Aquilina, K, Cohen, N, Lane, JD, Thoresen, M, Hanley, J, Randall, A & Case, CP 2014, 'Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions', Experimental Neurology, vol. 261, pp. 386-395. https://doi.org/10.1016/j.expneurol.2014.05.003
Curtis, Daniel J. ; Sood, Aman ; ica, H. L. ; Phillips, Tom J. ; Nishiguchi, Akihiro ; Leinster, Veron H L ; Coyle, Christopher ; Lacharme-Lora, Lizeth ; Beaumont, Oliver ; Kemp, Helena ; Goodall, Roberta ; Cornes, Leila ; Giugliano, Michele ; Barone, Rocco A. ; Matsusaki, Michiya ; Akashi, Mitsuru ; Tanaka, Hiroyoshi ; Kano, Mitsunobu ; McGarvey, Jennifer ; Halemani, Nagaraj D. ; Simon, Katja ; Keehan, Robert ; Ind, William ; Masters, Tracey ; Grant, Simon ; Athwal, Sharan ; Collett, Gavin ; Tannetta, Dionne ; Sargent, Ian L. ; Scull-Brown, Emma ; Liu, Xun ; Aquilina, Kristian ; Cohen, Nicki ; Lane, Jon D. ; Thoresen, Marianne ; Hanley, Jon ; Randall, Andrew ; Case, C. Patrick. / Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions. In: Experimental Neurology. 2014 ; Vol. 261. pp. 386-395.
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AU - Nishiguchi, Akihiro

AU - Leinster, Veron H L

AU - Coyle, Christopher

AU - Lacharme-Lora, Lizeth

AU - Beaumont, Oliver

AU - Kemp, Helena

AU - Goodall, Roberta

AU - Cornes, Leila

AU - Giugliano, Michele

AU - Barone, Rocco A.

AU - Matsusaki, Michiya

AU - Akashi, Mitsuru

AU - Tanaka, Hiroyoshi

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AU - McGarvey, Jennifer

AU - Halemani, Nagaraj D.

AU - Simon, Katja

AU - Keehan, Robert

AU - Ind, William

AU - Masters, Tracey

AU - Grant, Simon

AU - Athwal, Sharan

AU - Collett, Gavin

AU - Tannetta, Dionne

AU - Sargent, Ian L.

AU - Scull-Brown, Emma

AU - Liu, Xun

AU - Aquilina, Kristian

AU - Cohen, Nicki

AU - Lane, Jon D.

AU - Thoresen, Marianne

AU - Hanley, Jon

AU - Randall, Andrew

AU - Case, C. Patrick

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