This is a first time Phase I application to investigate the stability and viability of hNT neurons exposed to lithium to increase DA-type phenotype. hNT neurons are postmitotic, terminally differentiated human neurons which can be used in transplant procedures for such diseases as Parkinson's. These neurons can express DA which make them a viable alternative to fetal tissue for such implants, however, the rate of DA expression is not high in these neurons. The rate can be increased significantly by exposure to LiCl. This proposal will determine whether the increased expression of TH is indicative of true functional DA phenotype and whether the phenotype continues to be expressed in an animal model of PD.
If this is shown to be the case then we will potentially have a highly dopaminergic cell that is available in large quantities that can replace fetal tissue for neural transplantation treatments in Parkinson's disease.
| Newcomb, J D; Janowski, M; Zigova, T et al. (2007) A comparison of dopaminergic cells from the human NTera2/D1 cell line transplanted into the hemiparkinsonian rat. Life Sci 81:441-8 |
| Willing, Alison E; Zigova, Tanja; Milliken, Melissa et al. (2002) Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat. Eur J Neurosci 16:2271-8 |
