Skip Navigation LinksHome > February 2011 - Volume 117 - Issue 2, Part 1 > Prevention of Learning Deficit in a Down Syndrome Model
Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e3182051ca5
Original Research

Prevention of Learning Deficit in a Down Syndrome Model

Incerti, Maddalena MD; Toso, Laura MD; Vink, Joy MD; Roberson, Robin; Nold, Christopher MD; Abebe, Daniel; Spong, Catherine Y. MD

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Abstract

OBJECTIVE: To evaluate whether peptides given to adult mice with Down syndrome prevent learning deficits, and to delineate the mechanisms behind the protective effect.

METHODS: Ts65Dn mice were treated for 9 days with peptides D-NAPVSIPQ (NAP)+D-SALLRSIPA (SAL) or placebo, and wild-type animals were treated with placebo. Beginning on treatment day 4, the mice were tested for learning using the Morris watermaze. Probe tests for long-term memory were performed on treatment day 9 and 10 days after treatment stopped. Open-field testing was performed before and after the treatment. Calibrator-normalized relative real-time polymerase chain reaction (PCR) with glyceraldehyde-3-phosphate dehydrogenase (GAPD) standardization was performed on the whole brain and hippocampus for activity-dependent neuroprotective protein, vasoactive intestinal peptide (VIP), glial fibrillary acidic protein (GFAP), NR2B, NR2A, and γ-aminobutyric acid type A (GABAA)-α5. Statistics included analysis of variance and the Fisher protected least significant difference, with P<.05 significant.

RESULTS: The Ts65Dn plus placebo animals did not learn over the 5-day period compared with the controls (P<.001). The Ts65Dn +(D-NAP+D-SAL) learned significantly better than the Ts65Dn plus placebo (P<.05), and they retained learning similar to controls on treatment day 9, but not after 10 days of no treatment. Treatment with D-NAP+D-SAL prevented the Ts65Dn hyperactivity. Adult administration of D-NAP+D-SAL prevented changes in activity-dependent neuroprotective protein, intestinal peptide, and NR2B with levels similar to controls (all P<.05).

CONCLUSION: Adult treatment with D-NAP+D-SAL prevented learning deficit in Ts65Dn, a model of Down syndrome. Possible mechanisms of action include reversal of vasoactive intestinal peptide and activity-dependent neuroprotective protein dysregulation, as well as increasing expression of NR2B, thus facilitating learning.

© 2011 by The American College of Obstetricians and Gynecologists.

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