Prenatal Treatment Prevents Learning Deficit in Down Syndrome Model

Maddalena Incerti, Kari Horowitz, Robin Roberson, Daniel Abebe, Laura Toso, Madeline Caballero, Catherine Y. Spong

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Down syndrome is the most common genetic cause of mental retardation. Active fragments of neurotrophic factors release by astrocyte under the stimulation of vasoactive intestinal peptide, NAPVSIPQ (NAP) and SALLRSIPA (SAL) respectively, have shown therapeutic potential for developmental delay and learning deficits. Previous work demonstrated that NAP+SAL prevent developmental delay and glial deficit in Ts65Dn that is a well-characterized mouse model for Down syndrome. The objective of this study is to evaluate if prenatal treatment with these peptides prevents the learning deficit in the Ts65Dn mice. Pregnant Ts65Dn female and control pregnant females were randomly treated (intraperitoneal injection) on pregnancy days 8 through 12 with saline (placebo) or peptides (NAP 20 μg +SAL 20 μg) daily. Learning was assessed in the offspring (8-10 months) using the Morris Watermaze, which measures the latency to find the hidden platform (decrease in latency denotes learning). The investigators were blinded to the prenatal treatment and genotype. Pups were genotyped as trisomic (Down syndrome) or euploid (control) after completion of all tests. Statistical analysis: two-way ANOVA followed by Neuman-Keuls test for multiple comparisons, P<0.05 was used to denote statistical significance. Trisomic mice who prenatally received placebo (Down syndrome -placebo; n = 11) did not demonstrate learning over the five day period. DS mice that were prenatally exposed to peptides (Down syndrome-peptides; n = 10) learned significantly better than Down syndrome -placebo (p<0.01), and similar to control-placebo (n = 33) and control-peptide (n = 30). In conclusion prenatal treatment with the neuroprotective peptides (NAP+SAL) prevented learning deficits in a Down syndrome model. These findings highlight a possibility for the prevention of sequelae in Down syndrome and suggest a potential pregnancy intervention that may improve outcome.

Original languageEnglish (US)
Article numbere50724
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 29 2012
Externally publishedYes

Fingerprint

Down syndrome
Down Syndrome
learning
Learning
Peptides
placebos
peptides
Placebos
trisomics
Vasoactive Intestinal Peptide
Nerve Growth Factors
Therapeutics
Analysis of variance (ANOVA)
Statistical methods
mice
pregnancy
vasoactive intestinal peptide
Pregnancy
neurotrophins
SALLRSIPA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Incerti, M., Horowitz, K., Roberson, R., Abebe, D., Toso, L., Caballero, M., & Spong, C. Y. (2012). Prenatal Treatment Prevents Learning Deficit in Down Syndrome Model. PloS one, 7(11), [e50724]. https://doi.org/10.1371/journal.pone.0050724

Prenatal Treatment Prevents Learning Deficit in Down Syndrome Model. / Incerti, Maddalena; Horowitz, Kari; Roberson, Robin; Abebe, Daniel; Toso, Laura; Caballero, Madeline; Spong, Catherine Y.

In: PloS one, Vol. 7, No. 11, e50724, 29.11.2012.

Research output: Contribution to journalArticle

Incerti, M, Horowitz, K, Roberson, R, Abebe, D, Toso, L, Caballero, M & Spong, CY 2012, 'Prenatal Treatment Prevents Learning Deficit in Down Syndrome Model', PloS one, vol. 7, no. 11, e50724. https://doi.org/10.1371/journal.pone.0050724
Incerti M, Horowitz K, Roberson R, Abebe D, Toso L, Caballero M et al. Prenatal Treatment Prevents Learning Deficit in Down Syndrome Model. PloS one. 2012 Nov 29;7(11). e50724. https://doi.org/10.1371/journal.pone.0050724
Incerti, Maddalena ; Horowitz, Kari ; Roberson, Robin ; Abebe, Daniel ; Toso, Laura ; Caballero, Madeline ; Spong, Catherine Y. / Prenatal Treatment Prevents Learning Deficit in Down Syndrome Model. In: PloS one. 2012 ; Vol. 7, No. 11.
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