Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain.
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.
Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. soheil_falsafi@yahoo.com.
Soheil Keihan
SK
Falsafi
Genes and Disease Program, Center for Genomic Regulation and CIBERER, Barcelona, Spain.
Mara
M
Dierssen
Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Maryam
M
Ghafari
Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Arnold
A
Pollak
Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. gert.lubec@meduniwien.ac.at.
Gert
G
Lubec
D001921:Brain / Q000196:embryology / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005865:Gestational Age; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter
Brain receptors; Dopamine receptor; Fetal Down syndrome; Receptor complexes