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

23 Citations (Scopus)

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

Fingerprint

Down Syndrome
Learning
Placebos
Vasoactive Intestinal Peptide
Therapeutics
Aminobutyrates
Peptides
Glyceraldehyde-3-Phosphate Dehydrogenases
Proteins
Wild Animals
Long-Term Memory
Glial Fibrillary Acidic Protein
Real-Time Polymerase Chain Reaction
Hippocampus
Analysis of Variance
SALLRSIPA
Brain

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

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

Prevention of learning deficit in a down syndrome model. / Incerti, Maddalena; Toso, Laura; Vink, Joy; Roberson, Robin; Nold, Christopher; Abebe, Daniel; Spong, Catherine Y.

In: Obstetrics and gynecology, Vol. 117, No. 2, 02.2011, p. 354-361.

Research output: Contribution to journalArticle

Incerti, M, Toso, L, Vink, J, Roberson, R, Nold, C, Abebe, D & Spong, CY 2011, 'Prevention of learning deficit in a down syndrome model', Obstetrics and gynecology, vol. 117, no. 2, pp. 354-361. https://doi.org/10.1097/AOG.0b013e3182051ca5
Incerti M, Toso L, Vink J, Roberson R, Nold C, Abebe D et al. Prevention of learning deficit in a down syndrome model. Obstetrics and gynecology. 2011 Feb;117(2):354-361. https://doi.org/10.1097/AOG.0b013e3182051ca5
Incerti, Maddalena ; Toso, Laura ; Vink, Joy ; Roberson, Robin ; Nold, Christopher ; Abebe, Daniel ; Spong, Catherine Y. / Prevention of learning deficit in a down syndrome model. In: Obstetrics and gynecology. 2011 ; Vol. 117, No. 2. pp. 354-361.
@article{b559c3fe0f5e467db937d8a58d4ddaac,
title = "Prevention of learning deficit in a down syndrome model",
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.",
author = "Maddalena Incerti and Laura Toso and Joy Vink and Robin Roberson and Christopher Nold and Daniel Abebe and Spong, {Catherine Y.}",
year = "2011",
month = "2",
doi = "10.1097/AOG.0b013e3182051ca5",
language = "English (US)",
volume = "117",
pages = "354--361",
journal = "Obstetrics and Gynecology",
issn = "0029-7844",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Prevention of learning deficit in a down syndrome model

AU - Incerti, Maddalena

AU - Toso, Laura

AU - Vink, Joy

AU - Roberson, Robin

AU - Nold, Christopher

AU - Abebe, Daniel

AU - Spong, Catherine Y.

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79251556835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251556835&partnerID=8YFLogxK

U2 - 10.1097/AOG.0b013e3182051ca5

DO - 10.1097/AOG.0b013e3182051ca5

M3 - Article

C2 - 21252750

AN - SCOPUS:79251556835

VL - 117

SP - 354

EP - 361

JO - Obstetrics and Gynecology

JF - Obstetrics and Gynecology

SN - 0029-7844

IS - 2

ER -