Prenatal NAP+SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-D-aspartic acid and γ-aminobutyric acid receptors.

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 γ-aminobutyric acid (GABA) receptor subunits. Study Design: 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_Aα5 and GABA_Aβ3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. Results: NR2A, NR2B, and GABA_Aβ3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP+SAL increased NR2A, NR2B, and GABA_Aβ3 to levels similar to control (all P < .05). A significant difference in GABA_Aα5 levels was not found. Conclusion: Prenatal NAP+SAL increases NR2A, NR2B, and GABA_Aβ3 expression in adult DS mice to levels similar to controls. This may explain how NAP+SAL improve developmental milestone achievement. [Copyright &y& Elsevier]