Intracerebral transplantation of neural stem cells combined with trehalose ingestion alleviates pathology in a mouse model of Huntington's disease.
The present investigation examined the neuroprotective benefits for combined trehalose administration with C17.2 neural stem cell transplantation in a transgenic mouse model of Huntington's disease (HD), R6/2. C17.2 neural stem cells have the potential of differentiating into a neuronal phenotype in vitro and have been shown to be effective in the treatment of a variety of lysosomal lipid storage disorders in the nervous system. In this study, we transplanted these cells into the lateral ventricle of R6/2 transgenic mice in order to examine the efficacy of using these cells for correcting the accumulated polyglutamine storage materials in HD. To improve efficacy, animals were fed with a diet rich in trehalose, which has been shown to be beneficial to retard aggregate formation. The combined treatment strategy not only decreased ubiquitin-positive aggregation in striatum, alleviated polyglutamine aggregation formation, and reduced striatal volume, but also extended life span in the R6/2 animal model. Behavioral evaluation showed that the combination treatment improved motor function. Statistical analysis revealed that the combination treatment was more effective than treatment with trehalose alone on the basis of the above biochemical and behavioral criteria. This study provides a strong a basis for further developing an effective therapeutic strategy for HD.
Yang
Chia-Ron
CR
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Yu
Robert K
RK
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D018737:Hand Strength / Q000502:physiology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D010455:Peptides / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D016019:Survival Analysis; D014199:Trehalose / Q000008:administration & dosage*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine; D014199:Trehalose