| 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 neurodegeneration indicate such therapy may be a viable option in diseases such as DS. Murine NPC (mNPC, C17.2 immortalized cell line) or saline was implanted bilaterally into the dorsal hippocampus of postnatal day 2 (PND 2) pups to explore the feasibility of early postnatal treatment in the Ts65Dn 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 (adult cohort) or 48 weeks (aged cohort). We found the implanted mNPC survived into up to one year and did not stimulate a long-term neuroimmune response. However, mNPC survival was not necessary to elicit cognitive changes. Remarkably, adult trisomic mice implanted with saline improved their performance to the level of disomic controls in both the Morris Water Maze and Conditioned Taste Avoidance (CTA). The implantation of mNPC in trisomic mice did not show the same level of improvement, but did improve their performance in the Plus Maze when compared to chance. Aged trisomic mice implanted with saline had an improvement in both the CTA and a Novel Object Recognition task, while trisomic mice implanted with mNPC improved only in the CTA. The benefit seen in trisomic animals treated with saline may be due to the implantation procedure itself. Collectively, our results constitute the first ever assessment of NPC in altering cognition in a DS model, and uncover novel insight into utilizing the window of opportunity that exists in DS. |
