Prevention of learning deficit in a down syndrome model

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

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)354-361
Number of pages8
JournalObstetrics and gynecology
Volume117
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    Incerti, M., Toso, L., Vink, J., Roberson, R., Nold, C., Abebe, D., & Spong, C. Y. (2011). Prevention of learning deficit in a down syndrome model. Obstetrics and gynecology, 117(2), 354-361. https://doi.org/10.1097/AOG.0b013e3182051ca5