Prevention of developmental delays in a down syndrome mouse model

Laura Toso, Irene Cameroni, Robin Roberson, Daniel Abebe, Stephanie Bissell, Catherine Y. Spong

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

OBJECTIVE:: To estimate whether prenatal treatment with neuroprotective peptides prevents the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome and to explore the peptides' effects on achievement of normal development. METHODS:: Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8-12. Offspring were tested from postnatal day 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup's treatment and genotype. The pup's genotype was determined after completion of all tests. Activity-dependent neurotrophic factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real-time polymerase chain reaction. RESULTS:: Trisomic mice achieved milestones with a significant delay in four of five motor and sensory milestones. Trisomic mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in three of four motor and one of four sensory milestones (P<.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent neurotrophic factor expression was significantly downregulated in the Ts65Dn brains compared with the controls, prenatal treatment with NAPVSIPQ+ SALLRSIPA prevented the activity-dependent neurotrophic factor decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+ SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the trisomic brains, whereas treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. CONCLUSION:: Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome.

Original languageEnglish (US)
Pages (from-to)1242-1251
Number of pages10
JournalObstetrics and gynecology
Volume112
Issue number6
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Down Syndrome
Neuroglia
Vasoactive Intestinal Peptide
Glial Fibrillary Acidic Protein
Genotype
Therapeutics
Brain
Down-Regulation
Peptides
SALLRSIPA
Real-Time Polymerase Chain Reaction
Up-Regulation
Placebos
Research Personnel
Pregnancy
activity-dependent neurotrophic factor

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Prevention of developmental delays in a down syndrome mouse model. / Toso, Laura; Cameroni, Irene; Roberson, Robin; Abebe, Daniel; Bissell, Stephanie; Spong, Catherine Y.

In: Obstetrics and gynecology, Vol. 112, No. 6, 01.12.2008, p. 1242-1251.

Research output: Contribution to journalArticle

Toso, L, Cameroni, I, Roberson, R, Abebe, D, Bissell, S & Spong, CY 2008, 'Prevention of developmental delays in a down syndrome mouse model', Obstetrics and gynecology, vol. 112, no. 6, pp. 1242-1251. https://doi.org/10.1097/AOG.0b013e31818c91dc
Toso, Laura ; Cameroni, Irene ; Roberson, Robin ; Abebe, Daniel ; Bissell, Stephanie ; Spong, Catherine Y. / Prevention of developmental delays in a down syndrome mouse model. In: Obstetrics and gynecology. 2008 ; Vol. 112, No. 6. pp. 1242-1251.
@article{00c5852855c24b9ab57ecff1682ab457,
title = "Prevention of developmental delays in a down syndrome mouse model",
abstract = "OBJECTIVE:: To estimate whether prenatal treatment with neuroprotective peptides prevents the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome and to explore the peptides' effects on achievement of normal development. METHODS:: Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8-12. Offspring were tested from postnatal day 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup's treatment and genotype. The pup's genotype was determined after completion of all tests. Activity-dependent neurotrophic factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real-time polymerase chain reaction. RESULTS:: Trisomic mice achieved milestones with a significant delay in four of five motor and sensory milestones. Trisomic mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in three of four motor and one of four sensory milestones (P<.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent neurotrophic factor expression was significantly downregulated in the Ts65Dn brains compared with the controls, prenatal treatment with NAPVSIPQ+ SALLRSIPA prevented the activity-dependent neurotrophic factor decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+ SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the trisomic brains, whereas treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. CONCLUSION:: Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome.",
author = "Laura Toso and Irene Cameroni and Robin Roberson and Daniel Abebe and Stephanie Bissell and Spong, {Catherine Y.}",
year = "2008",
month = "12",
day = "1",
doi = "10.1097/AOG.0b013e31818c91dc",
language = "English (US)",
volume = "112",
pages = "1242--1251",
journal = "Obstetrics and Gynecology",
issn = "0029-7844",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Prevention of developmental delays in a down syndrome mouse model

AU - Toso, Laura

AU - Cameroni, Irene

AU - Roberson, Robin

AU - Abebe, Daniel

AU - Bissell, Stephanie

AU - Spong, Catherine Y.

PY - 2008/12/1

Y1 - 2008/12/1

N2 - OBJECTIVE:: To estimate whether prenatal treatment with neuroprotective peptides prevents the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome and to explore the peptides' effects on achievement of normal development. METHODS:: Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8-12. Offspring were tested from postnatal day 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup's treatment and genotype. The pup's genotype was determined after completion of all tests. Activity-dependent neurotrophic factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real-time polymerase chain reaction. RESULTS:: Trisomic mice achieved milestones with a significant delay in four of five motor and sensory milestones. Trisomic mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in three of four motor and one of four sensory milestones (P<.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent neurotrophic factor expression was significantly downregulated in the Ts65Dn brains compared with the controls, prenatal treatment with NAPVSIPQ+ SALLRSIPA prevented the activity-dependent neurotrophic factor decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+ SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the trisomic brains, whereas treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. CONCLUSION:: Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome.

AB - OBJECTIVE:: To estimate whether prenatal treatment with neuroprotective peptides prevents the developmental delay and the glial deficit in the Ts65Dn mouse model for Down syndrome and to explore the peptides' effects on achievement of normal development. METHODS:: Pregnant Ts65Dn females were randomly assigned to NAPVSIPQ+SALLRSIPA or control and were treated by investigators blinded to treatment and genotype on gestational days 8-12. Offspring were tested from postnatal day 5 to 21 for motor and sensory milestones with standardized tests by operators blinded to the pup's treatment and genotype. The pup's genotype was determined after completion of all tests. Activity-dependent neurotrophic factor, glial fibrillary acidic protein, and vasoactive intestinal peptide expression were determined using real-time polymerase chain reaction. RESULTS:: Trisomic mice achieved milestones with a significant delay in four of five motor and sensory milestones. Trisomic mice that were prenatally exposed to NAPVSIPQ+SALLRSIPA achieved developmental milestones at the same time as the controls in three of four motor and one of four sensory milestones (P<.01). Euploid pups prenatally treated with NAPVSIPQ+SALLRSIPA achieved developmental milestones significantly earlier than the euploid pups prenatally treated with placebo. Activity-dependent neurotrophic factor expression was significantly downregulated in the Ts65Dn brains compared with the controls, prenatal treatment with NAPVSIPQ+ SALLRSIPA prevented the activity-dependent neurotrophic factor decrease in the Ts65Dn brains, and the expression was not different from the controls. The glial marker glial fibrillary acidic protein demonstrated the known glial deficit in the Ts65Dn mice, and treatment with NAPVSIPQ+ SALLRSIPA prevented its downregulation. Lastly, vasoactive intestinal peptide levels were increased in the trisomic brains, whereas treatment with NAPVSIPQ+SALLRSIPA did not prevent its upregulation. CONCLUSION:: Prenatal treatment with NAPVSIPQ and SALLRSIPA prevented developmental delay and the glial deficit in Down syndrome. These findings highlight a possibility for the prevention of developmental sequelae in Down syndrome and suggest a potential intervention during pregnancy that may improve the outcome.

UR - http://www.scopus.com/inward/record.url?scp=58849116434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58849116434&partnerID=8YFLogxK

U2 - 10.1097/AOG.0b013e31818c91dc

DO - 10.1097/AOG.0b013e31818c91dc

M3 - Article

C2 - 19037032

AN - SCOPUS:58849116434

VL - 112

SP - 1242

EP - 1251

JO - Obstetrics and Gynecology

JF - Obstetrics and Gynecology

SN - 0029-7844

IS - 6

ER -