title: Induction of GAP-43 modulates neuroplasticity in PBSC (CD34+) implanted-Parkinson's model.
abstract: 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.
authors.affiliation: Department of Neurology, Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Li
authors.forename: Hsiao-Fen
authors.initials: HF
authors.lastname: Peng
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Hsiao-Jung
authors.initials: HJ
authors.lastname: Wang
authors.forename: Ching-Yuan
authors.initials: CY
authors.lastname: Su
authors.forename: Yih-Jing
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: 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
chemical_list: 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