Abstract |
We have investigated the effectiveness of transplantation of human neural stem cells into adult rat striatum prior to induction of striatal damage with the mitochondrial toxin 3-nitropropionic acid (3-NP). Systemic 3-NP administration caused widespread neuropathological deficits similar to ones found in Huntington disease (HD) including impairment in motor function (rotarod balance test) and extensive degeneration of neuron-specific nuclear antigen (NeuN)(+) neurons, calbindin(+) neurons and glutamic acid decarboxylase (GAD)(+) striatal neurons. Animals receiving intrastriatal implantation of human neural stem cells (hNSCs) 1 week before 3-NP treatments exhibited significantly improved motor performance and reduced damage to striatal neurons compared with control sham injections. In contrast, transplantation of hNSCs at 12 h after the initial 3-NP administration did not lead to any improvement in motor performance or protect striatal neurons from the 3-NP-induced toxicity. These results indicate that the presence of grafted hNSCs before 3-NP treatment is required for host striatal neuronal protection and enhanced motor function. Immunoreactivity of brain-derived neurotrophic factor ( BDNF) was found in vitro in cultured hNSCs and in vivo in grafted NSCs with expression and secretion of BDNF demonstrated by RT-PCR, immunocytochemistry, dot-blot, and ELISA analyses. Thus, protective effects of proactive transplantation of hNSCs may be due, in part, to effects mediated by BDNF. The findings in this work have particular relevance to a rat model of HD in that proactive transplanted hNSCs protect host striatal neurons against neuronal injury and improve motor impairment induced by 3-NP toxicity.
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Authors | Jae K Ryu, Jean Kim, Sung J Cho, Kozo Hatori, Astushi Nagai, Hyun B Choi, Min C Lee, James G McLarnon, Seung U Kim |
Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 16
Issue 1
Pg. 68-77
(Jun 2004)
ISSN: 0969-9961 [Print] United States |
PMID | 15207263
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Animals
- Cell Line, Transformed
- Corpus Striatum
(pathology, transplantation)
- Disease Models, Animal
- Humans
- Huntington Disease
(pathology, surgery)
- Male
- Nerve Degeneration
(pathology, prevention & control, surgery)
- Neurons
(transplantation)
- Rats
- Rats, Inbred Lew
- Stem Cell Transplantation
(methods)
- Stem Cells
(physiology)
- Telencephalon
(transplantation)
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