title: GDNF-pretreatment enhances the survival of neural stem cells following transplantation in a rat model of Parkinson's disease.
abstract: Cell transplantation has been shown to be an effective therapy for central nervous system disorders in animal models. Improving the efficacy of cell transplantation depends critically on improving grafted cell survival. We investigated whether glial cell line-derived neurotrophic factor (GDNF)-pretreatment of neural stem cells (NSCs) enhanced grafted cell survival in a rat model of Parkinson's disease (PD). We first examined the neuroprotective effects of GDNF on oxygen-glucose deprivation (OGD) in NSCs. Cells were pretreated with GDNF for 3 days before subjecting them to OGD. After 12h of OGD, GDNF-pretreated NSCs showed significant increases in survival rates compared with PBS-pretreated NSCs. An apoptosis assay showed that the number of apoptotic cells was significantly decreased in GDNF-pretreated NSCs at 1h and 6h after OGD. A PD rat model was then established by unilateral injection of 6-hydroxydopamine (6-OHDA, 9μg) into the medial forebrain bundle. Two weeks after 6-OHDA injection, GDNF-pretreated NSCs, PBS-pretreated NSCs, or PBS were injected into PD rat striatum. The survival of grafted cells in the striatum was significantly increased in the GDNF-pretreated NSC group compared with the control groups. GDNF pretreatment increased survival of NSCs following transplantation, at least partly through suppression of cell apoptosis.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan. gmd19011@s.okayama-u.ac.jp
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Kameda
authors.forename: T
authors.initials: T
authors.lastname: Yasuhara
authors.forename: N
authors.initials: N
authors.lastname: Tajiri
authors.forename: Y
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: H B
authors.initials: HB
authors.lastname: Liang
authors.forename: J T
authors.initials: JT
authors.lastname: Tayra
authors.forename: A
authors.initials: A
authors.lastname: Shinko
authors.forename: T
authors.initials: T
authors.lastname: Wakamori
authors.forename: T
authors.initials: T
authors.lastname: Agari
authors.forename: I
authors.initials: I
authors.lastname: Date
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000502:physiology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016627:Oxidopamine