title: Effects of neonatal neural progenitor cell implantation on adult neuroanatomy and cognition in the Ts65Dn model of Down syndrome.
abstract: As much of the aberrant neural development in Down syndrome (DS) occurs postnatally, an early opportunity exists to intervene and influence life-long cognitive development. Recent success using neural progenitor cells (NPC) in models of adult neurodegeneration indicate such therapy may be a viable option in diseases such as DS. Murine NPC (mNPC, C17.2 cell line) or saline were implanted bilaterally into the dorsal hippocampus of postnatal day 2 (PND 2) Ts65Dn pups to explore the feasibility of early postnatal treatment in this mouse model of DS. Disomic littermates provided karyotype controls for trisomic pups. Pups were monitored for developmental milestone achievement, and then underwent adult behavior testing at 14 weeks of age. We found that implanted mNPC survived into adulthood and migrated beyond the implant site in both karyotypes. The implantation of mNPC resulted in a significant increase in the density of dentate granule cells. However, mNPC implantation did not elicit cognitive changes in trisomic mice either neonatally or in adulthood. To the best of our knowledge, these results constitute the first assessment of mNPC as an early intervention on cognitive ability in a DS model.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Rachubinski
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Crowley
authors.forename: John R
authors.initials: JR
authors.lastname: Sladek
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Maclean
authors.forename: Kimberly B
authors.initials: KB
authors.lastname: Bjugstad
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002452:Cell Count; D002454:Cell Differentiation; D048429:Cell Size; D002470:Cell Survival; D003071:Cognition / Q000502:physiology*; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D004327:Drinking Behavior; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology*; D015213:Neuroimmunomodulation; D033581:Stem Cell Transplantation
chemical_list: D049452:Green Fluorescent Proteins