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Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain

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Abstract

In this study, cortical receptor complex levels were determined in fetal Down syndrome (DS, trisomy 21) brain. Frontal cortices were obtained from individuals with DS (19th–22nd week of gestation) and controls. Membrane proteins were extracted, assayed on blue native gels and immunoblotted with brain receptor antibodies. Levels of a D1R-containing complex were markedly decreased in male and female cortices of DS individuals. Females with DS had significant reductions of nicotinic acetylcholine receptors α4 and α7, NMDA receptor GluN1 and AMPA receptor GluA1- and GluA3-containing receptor complexes. Levels of other brain receptor complexes (5-hydroxytryptamine 1A, GluA2 and GluR4 receptor-containing complexes) were comparable between the groups of females. Levels of GluA2- and GluA3-containing complexes were significantly increased in males. Decreased levels of D1R complexes in both sexes, along with the significant reduction of α4, α7-containing receptor complexes observed in females, may explain the brain deficits and impaired cognition observed in DS.

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Acknowledgments

The human biospecimens used in this project were provided by the Fetal Tissue Bank of the Vall d’Hebron University Hospital Biobank with appropriate ethics approval. The work was partially supported by the Verein zur Durchführung der wissenschaftlichen Forschung auf dem Gebiet der Neonatologie und Kinder intensiv Medizin.

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    1. Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

      Soheil Keihan Falsafi, Maryam Ghafari, Arnold Pollak & Gert Lubec

    2. Genes and Disease Program, Center for Genomic Regulation and CIBERER, Barcelona, Spain

      Mara Dierssen

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    S. Keihan Falsafi, M. Dierssen and M. Ghafari contributed equally to the paper.

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    Keihan Falsafi, S., Dierssen, M., Ghafari, M. et al. Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain. Amino Acids 48, 103–116 (2016). https://doi.org/10.1007/s00726-015-2062-6

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