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.
Highlights
The British physician John Langdon Down first described Down syndrome (DS) almost 150 years ago [1]
By extrapolating from the average number of cells found per section to the total number of possible sections, an estimated 5.56% of implanted murine NPC (mNPC) survived in disomic brains
The distribution of green fluorescent protein (GFP)+ mNPC in the hippocampus was similar between karyotypes, the GFP+ cells were found in the pyramidal layers of disomic brains (Figure 1b) more often than in trisomic brains (Figure 2a,b)
Summary
The British physician John Langdon Down first described Down syndrome (DS) almost 150 years ago [1]. DS is the most common genetic cause of intellectual disability and occurs in 1 in every 766 live births [2]. While other medical conditions associated with DS are treatable, intellectual disability remains the most limiting factor. No treatment can influence the proper cognitive development in DS and provide lifelong cognitive improvements. The potential of a neonatal intervention is appealing in DS, because many of the neuroanatomical abnormalities associated with DS have yet to develop. Small alterations in early development could affect the lifelong trajectory of development in the DS brain
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