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Ascorbic Acid Increases the Number of Dopamine Neurons In Vitro and in Transplants to the 6-OHDA-Lesioned Rat Brain

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Abstract:

The inadequate survival of dopamine neurons following intracerebral transplantation is in part attributed to the generation of reactive oxygen species and subsequent oxidative stress. To address this, we investigated whether the antioxidant ascorbic acid (vitamin C) had any effect on the yields of dopamine neurons derived from E14 rat ventral mesencephalic cells in vitro and in grafts. Following in vitro differentiation in medium containing ascorbic acid at concentrations ranging from 20 to 100 M, significantly more neurons were immunopositive for the marker of mesencephalic dopamine neurons, tyrosine hydroxylase (TH), when compared to standard differentiation conditions containing no ascorbic acid. Mesencephalic cell suspensions supplemented with 100 M ascorbic acid were also transplanted into unilateral 6-OHDA-lesioned rats and behavioral rotation was assessed at 2, 4, and 6 weeks posttransplantation. Grafts pretreated with ascorbic acid contained significantly more surviving dopamine neurons compared to nontreated grafts. However, no significant difference in rotation score was observed, with both groups showing a reversal and overcompensation of rotational bias. In addition, no evidence of neurogenesis of nigral dopamine neurons was observed in transplant groups. While the increased number of dopamine neurons observed in our study following ascorbic acid treatment may reflect a selective survival effect, our in vitro results suggest that ascorbic acid may act to increase the number dopamine neurons, both in culture and following transplantation, by stimulating dopaminergic differentiation of neural precursors from the fetal ventral mesencephalon.

Keywords: Ascorbic acid; Dopaminergic neurons; Neuronal survival; Oxidative stress; Parkinson's disease; Transplantation

Document Type: Research Article

DOI: https://doi.org/10.3727/096368908786516774

Publication date: 2008-07-01

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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