Neural Stem Cells Reduce Hippocampal Tau and Reelin Accumulation in Aged Ts65Dn down Syndrome Mice

Cell Transplantation

Article

H. Jiang¹  K. B. Bjugstad¹  K. N. Maclean¹  D. S. Kern¹  J. R. Sladek²  E. Y. Synder³ 

[1] Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA;Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA; Department of Neurology, University of Colorado Denver, Aurora, CO, USA;Program in Stem Cell and Regenerative Biology, Burnham Institute for Medical Research, La Jolla, CA, USA;

关键词: Tau;    Down syndrome;    Alzheimer's disease;    Neural stem cells;    Ts65Dn mice;    Reelin;   

DOI  :  10.3727/096368910X528085

 received in 2010-06-21, accepted in 2010-08-02,  发布年份 2011

来源: Sage Journals

【 摘 要 】

Tau accumulation, in the form of neurofibrillary tangles (NFT), is an early neuropathological characteristic of Alzheimer's disease (AD) and early onset AD frequently seen in Down syndrome (DS). We investigated the presence of tau accumulation in the brains of aging DS mice using the Ts65Dn mouse model. All aged mice appeared to have substantial clusters of extracellular granules that were positive for tau and reelin, but not for amyloid-β or APP. These clusters were found primarily in CA1 of the hippocampus. In addition, the aged trisomic DS mice had a significantly greater accumulation of extracellular tau/reelin granular deposits compared to disomic littermates. These granules were similar to those described by others who also found extracelluar proteinous granules in the brains of non-DS mice engineered to model aging and/or AD. When neural stem cells (NSC) were implanted unilaterally into the hippocampus of the Ts65Dn mice, the tau/reelin-positive granules were significantly reduced in both trisomic and disomic mice. Our findings indicate that changes in tau/reelin-positive granules could be used as an index for neuropathological assessment in aging DS and AD. Furthermore, changes in granule density could be used to test the efficacy of novel treatments, such as NSC implantation. Lastly, it is speculated that the unique abilities of NSC to migrate and express growth factors might be a contributing factor to reducing tau/reelin accumulation in aging DS and AD.

【 授权许可】

Unknown   
© 2011 Cognizant Comm. Corp.

【 图 表 】

Figure 2.