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

Joy Vink, Maddelena Incerti, Laura Toso, Robin Roberson, Daniel Abebe, Catherine Y. Spong

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 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 GABAAα5 and GABAAβ3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. Results: NR2A, NR2B, and GABAAβ3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP+SAL increased NR2A, NR2B, and GABAAβ3 to levels similar to control (all P < .05). A significant difference in GABAAα5 levels was not found. Conclusion: Prenatal NAP+SAL increases NR2A, NR2B, and GABAAβ3 expression in adult DS mice to levels similar to controls. This may explain how NAP+SAL improve developmental milestone achievement.

Original languageEnglish (US)
Pages (from-to)524.e1-524.e4
JournalAmerican journal of obstetrics and gynecology
Volume200
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Fingerprint

Aminobutyrates
N-Methylaspartate
Down Syndrome
Glyceraldehyde-3-Phosphate Dehydrogenases
GABA Receptors
Adult Children
SALLRSIPA
gamma-Aminobutyric Acid
Real-Time Polymerase Chain Reaction
Analysis of Variance
Placebos
Brain

Keywords

  • Down syndrome
  • learning
  • N-methyl-D-aspartic acid
  • NAPVSIPQ
  • SALLRSIPA
  • Ts65Dn
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

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. / Vink, Joy; Incerti, Maddelena; Toso, Laura; Roberson, Robin; Abebe, Daniel; Spong, Catherine Y.

In: American journal of obstetrics and gynecology, Vol. 200, No. 5, 05.2009, p. 524.e1-524.e4.

Research output: Contribution to journalArticle

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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 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 GABAAα5 and GABAAβ3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. Results: NR2A, NR2B, and GABAAβ3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP+SAL increased NR2A, NR2B, and GABAAβ3 to levels similar to control (all P < .05). A significant difference in GABAAα5 levels was not found. Conclusion: Prenatal NAP+SAL increases NR2A, NR2B, and GABAAβ3 expression in adult DS mice to levels similar to controls. This may explain how NAP+SAL improve developmental milestone achievement.",
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T1 - 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

AU - Vink, Joy

AU - Incerti, Maddelena

AU - Toso, Laura

AU - Roberson, Robin

AU - Abebe, Daniel

AU - Spong, Catherine Y.

PY - 2009/5

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N2 - 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 GABAAα5 and GABAAβ3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. Results: NR2A, NR2B, and GABAAβ3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP+SAL increased NR2A, NR2B, and GABAAβ3 to levels similar to control (all P < .05). A significant difference in GABAAα5 levels was not found. Conclusion: Prenatal NAP+SAL increases NR2A, NR2B, and GABAAβ3 expression in adult DS mice to levels similar to controls. This may explain how NAP+SAL improve developmental milestone achievement.

AB - 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 GABAAα5 and GABAAβ3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. Results: NR2A, NR2B, and GABAAβ3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP+SAL increased NR2A, NR2B, and GABAAβ3 to levels similar to control (all P < .05). A significant difference in GABAAα5 levels was not found. Conclusion: Prenatal NAP+SAL increases NR2A, NR2B, and GABAAβ3 expression in adult DS mice to levels similar to controls. This may explain how NAP+SAL improve developmental milestone achievement.

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