title: Prenatal NAP+SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-D-aspartic acid and gamma-aminobutyric acid receptors.
abstract: OBJECTIVE
  Down syndrome (DS) affects 1/800 infants. Prenatal NAPVSIPQ (NAP) and SALLRSIPA (SAL) (NAP+SAL) prevent developmental delay in Ts65Dn mice, a mouse model of DS. We investigated whether this finding involves N-methyl-D-aspartic acid and gamma-aminobutyric acid (GABA) receptor subunits.
  
  
  METHODS
  Pregnant Ts65Dn mice were treated with placebo or NAP+SAL on gestational days 8-12. After developmental delay prevention was shown, 4 trisomic (Ts), 4 control, and 3 Ts+NAP+SAL adult offspring brains (from 3 litters) were collected. Calibrator-normalized real-time polymerase chain reaction was performed using primers for N-methyl-D-aspartic acid subunits NR2A and NR2B, and for GABA subunits GABA(A)alpha5 and GABA(A)beta3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant.
  
  
  RESULTS
  NR2A, NR2B, and GABA(A)beta3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP+SAL increased NR2A, NR2B, and GABA(A)beta3 to levels similar to control (all P < .05). A significant difference in GABA(A)alpha5 levels was not found.
  
  
  CONCLUSIONS
  Prenatal NAP+SAL increases NR2A, NR2B, and GABA(A)beta3 expression in adult DS mice to levels similar to controls. This may explain how NAP+SAL improve developmental milestone achievement.
authors.affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Vink
authors.forename: Maddelena
authors.initials: M
authors.lastname: Incerti
authors.forename: Laura
authors.initials: L
authors.lastname: Toso
authors.forename: Robin
authors.initials: R
authors.lastname: Roberson
authors.forename: Daniel
authors.initials: D
authors.lastname: Abebe
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong