Induction of GAP-43 modulates neuroplasticity in PBSC (CD34+) implanted-Parkinson's model.
As a result of the progressive decrease in efficacy of drugs used to treat Parkinson's disease (PD) and the rapid development of motor complications, effective alternative treatments for PD are required. In a 6-hydroxydopamine (6-OHDA)-induced Parkinson's rat model, intracerebral peripheral blood stem cell (CD34(+)) (PBSC) transplantation significantly protected dopaminergic neurons from 6-OHDA-induced neurotoxicity, enhanced neural repair of tyrosine hydroxylase neurons through up-regulation of Bcl-2, facilitated stem cell plasticity, and attenuated activation of microglia, in comparison with vehicle-control rats. The 6-OHDA-lesioned hemi-Parkinsonian rats receiving intrastriatal transplantation of PBSCs also showed: 1) enhanced glucose metabolism in the lesioned striatum and thalamus, demonstrated by [(18)F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET), 2) improved neurochemical activity as shown by proton magnetic resonance spectroscopy ((1)H-MRS), and 3) significantly reduced rotational behavior in comparison with control lesioned rats. These observations might be explained by an up-regulation of growth-associated protein 43 (GAP-43) expression because improvements in neurological dysfunction were blocked by injection of MK-801 in the PBSC-treated group. In addition, a significant increase in neurotrophic factor expression was found in the ipsilateral hemisphere of the PBSC-treated group. In summary, this protocol may be a useful strategy for the treatment of clinical PD.
Shyu
Woei-Cherng
WC
Department of Neurology, Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan.
Li
Kuo-Wei
KW
Peng
Hsiao-Fen
HF
Lin
Shinn-Zong
SZ
Liu
Ren-Shyan
RS
Wang
Hsiao-Jung
HJ
Su
Ching-Yuan
CY
Lee
Yih-Jing
YJ
Li
Hung
H
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D003714:Denervation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18; D019922:GAP-43 Protein / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism
D018952:Antigens, CD34; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D019788:Fluorodeoxyglucose F18; D016627:Oxidopamine; D005947:Glucose; D004298:Dopamine