Document Detail


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.
MedLine Citation:
PMID:  19327737     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. 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(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. CONCLUSION: 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:
Joy Vink; Maddelena Incerti; Laura Toso; Robin Roberson; Daniel Abebe; Catherine Y Spong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2009-03-26
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  200     ISSN:  1097-6868     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-20     Completed Date:  2009-05-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  524.e1-4     Citation Subset:  AIM; IM    
Affiliation:
Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Brain Diseases / drug therapy*,  genetics,  prevention & control*
Central Nervous System / drug effects,  embryology,  growth & development
Disease Models, Animal
Down Syndrome / complications*,  genetics
Female
Mental Retardation / drug therapy,  prevention & control
Mice
Mice, Mutant Strains
Nerve Tissue Proteins / pharmacology*
Oligopeptides / pharmacology*
Peptide Fragments / pharmacology*
Pregnancy
Prenatal Exposure Delayed Effects
Receptors, GABA-A / genetics,  metabolism
Receptors, N-Methyl-D-Aspartate / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Gabra5 protein, mouse; 0/NAPVSIPQ peptide; 0/NR2A NMDA receptor; 0/NR2B NMDA receptor; 0/Nerve Tissue Proteins; 0/Oligopeptides; 0/Peptide Fragments; 0/Receptors, GABA-A; 0/Receptors, N-Methyl-D-Aspartate; 0/SALLRSIPA; 0/beta3 subunit, GABA-A receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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