title: Prenatal treatment prevents learning deficit in Down syndrome model.
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.
  
  
  METHODS
  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.
authors.affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development, Bethesda, Maryland, United States of America. maddalena.incerti@gmail.com
authors.forename: Maddalena
authors.initials: M
authors.lastname: Incerti
authors.forename: Kari
authors.initials: K
authors.lastname: Horowitz
authors.forename: Robin
authors.initials: R
authors.lastname: Roberson
authors.forename: Daniel
authors.initials: D
authors.lastname: Abebe
authors.forename: Laura
authors.initials: L
authors.lastname: Toso
authors.forename: Madeline
authors.initials: M
authors.lastname: Caballero
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000188:drug therapy*; D005260:Female; D007858:Learning / Q000187:drug effects*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011247:Pregnancy
chemical_list: D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; C526732:SALLRSIPA; C425904:davunetide