Abstract
Stem cell therapy is a promising treatment for incurable disorders including Huntington's disease (HD). Adipose-derived stem cell (ASC) is an easily available source of stem cells. Since ASCs can be differentiated into nervous stem cells, it has clinically feasible potential for neurodegenerative disease. In addition, ASCs secrete various anti-apoptotic growth factors, which improve the symptoms of disease from transplanted ASCs. Thus, cell-free extracts of ASCs (ASCs-E) could be a potential candidate for treatment of HD. Here, we investigated effects of ASCs-E on R6/2 HD mouse model and neuronal cells. In R6/2 HD model, injection of ASCs-E improved the performance in Rotarod test. ASCs-E also ameliorated striatal atrophy and mutant huntingtin aggregation in the striatum. In Western blot increased expressions of p-Akt, p-CREB and PGC1α were noted by injection of ASCs-E, when comparing to the R6/2 HD model. Neuro2A neuroblastoma cells treated with ASCs-E showed increased expression of p-CREB and PGC1α. In conclusion, ASCs-E delayed disease progression in animal model of HD by restoring of CREB-PGC1α pathway and could be a potential resource for treatment of HD.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adipocytes / chemistry
-
Adipocytes / metabolism*
-
Animals
-
Atrophy
-
Behavior, Animal / drug effects
-
Cell Extracts / administration & dosage
-
Cell Extracts / pharmacology*
-
Cell Line
-
Corpus Striatum / drug effects
-
Corpus Striatum / metabolism
-
Corpus Striatum / pathology
-
Cyclic AMP Response Element-Binding Protein / metabolism
-
Disease Models, Animal
-
Disease Progression
-
Female
-
Humans
-
Huntington Disease / metabolism*
-
Male
-
Mice
-
Neurons / drug effects
-
Neurons / metabolism
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
-
Phenotype
-
Proto-Oncogene Proteins c-akt / metabolism
-
Serotonin Plasma Membrane Transport Proteins / genetics
-
Serotonin Plasma Membrane Transport Proteins / metabolism
-
Stem Cells / chemistry
-
Stem Cells / metabolism*
-
Transcription Factors / metabolism
Substances
-
Cell Extracts
-
Cyclic AMP Response Element-Binding Protein
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
-
Ppargc1a protein, mouse
-
Serotonin Plasma Membrane Transport Proteins
-
Slc6a4 protein, mouse
-
Transcription Factors
-
Proto-Oncogene Proteins c-akt
Grants and funding
This work was supported by grants from the Korea Health 21 R& D Project, Ministry of Health & Welfare (A092058), WCU-Neurocytomics program and National Research Foundation of Korea (NRF) (2011-0012728). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.