Neuroprotective properties of cultured neural progenitor cells are associated with the production of sonic hedgehog

• Published in: Neuroscience Vol. 131; no. 4; pp. 899 - 916
• Main Authors: Rafuse, V.F., Soundararajan, P., Leopold, C., Robertson, H.A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2005; Elsevier
• Subjects: Animals; Antimetabolites; apoptosis; Biological and medical sciences; Blotting, Western; Bromodeoxyuridine; Cell Count; Cell Survival - physiology; Cells, Cultured; Chick Embryo; Culture Media, Conditioned; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - physiology; dopaminergic neurons; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hedgehog Proteins; Immunohistochemistry; Medical sciences; Mice; Mice, Transgenic; Movement Disorders - physiopathology; Movement Disorders - therapy; Neurology; Neurons - physiology; neuroprotection; Oxidopamine - toxicity; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson Disease - therapy; Parkinson’s disease; sonic hedgehog; Stem Cell Transplantation; stem cells; Stem Cells - physiology; Sympatholytics - toxicity; Trans-Activators - biosynthesis; Vertebrates: nervous system and sense organs; NPC; E; apoptosis; 6-OHDA; DMEM; DV; Shh; FBS; Shh-N; SVZ; IA; MBP; MSC; ML; PBS; stem cells; eGFP; EGF; bFGF; AP; GFAP; DIV; PD; neuroprotection; dopaminergic neurons; VM; sonic hedgehog; Dkk-1; SKP; HBSS; MPTP; Parkinson’s disease; BrdU; Ptc; ELISA; Neuroprotection; Nervous system diseases; Parkinson's disease; Stem cell; Precursor cell; Parkinson disease; In vitro; Cerebral disorder; Central nervous system disease; Dopaminergic neuron; Degenerative disease; Extrapyramidal syndrome; Apoptosis; Progenitor cell
• DOI: 10.1016/j.neuroscience.2004.11.048
• ISSN: 0306-4522

Numerous studies have shown that abnormal motor behavior improves when neural progenitor cells (NPCs) are transplanted into animal models of neurodegeneration. The mechanisms responsible for this improvement are not fully understood. Indirect anatomical evidence suggests that attention of abnormal motor behavior is attributed, at least in part, to the secretion of trophic factors from the transplanted NPCs. However, there is little direct evidence supporting this hypothesis. Here we show that NPCs isolated from the subventricular zone (SVZ) of neonatal mice are highly teratogenic when transplanted into the neural tube of developing chick embryos and are neuroprotective for fetal dopaminergic neurons in culture because they release sonic hedgehog (Shh). In addition, the neuroprotective properties of NPCs can be exploited to promote better long-term survival of transplanted fetal neurons in an animal model of Parkinson’s disease. Thus, cultured NPCs isolated from the SVZ can secrete at least one potent mitogen (Shh) that dramatically affects the fate of neighboring cells. This trait may account for some of the improvement in motor behavior often reported in animal models of neurodegeneration after transplantation of cultured NPCs that were isolated from the SVZ.