title: Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat.
abstract: Lithium (Li +) treatment of NTera2/D1 (or hNT Neurons) in culture increases tyrosine hydroxylase (TH) expression in this cell-line [Zigova et al., (1999) Exp. Neurol., 157, 251-258]. It is not known if these Li + treated cells maintain TH expression once transplanted into the striatum of the hemiparkinsonian rats. hNT neurons were either treated with 1 mm LiCl or left untreated and then transplanted into the striatum of Sprague-Dawley rats. Some cells were exposed to the lithium for 24 h in culture while others were exposed only briefly (2-3 h) just prior to transplantation. We also examined whether Li + treatment of the animal after transplantation (0.24% w/w lithium carbonate in chow) was effective in increasing neuronal survival. One week after transplantation, the animals were perfused with 4% paraformaldehyde and immunocytochemistry was performed on 30 micro m sections through the transplant. Human nuclear matrix antigen immunostaining demonstrated that there was significantly better survival of cells in the group treated briefly with lithium compared to all other groups. Brief exposure to lithium resulted in a greater expression of TH in situ as well. Neuron specific enolase immunohistochemistry showed that there was extensive fibre outgrowth in all groups. These results suggest that brief Li + exposure may enhance survival to over 60% and increase TH expression of hNT Neurons transplanted in the hemiparkinsonian rat nearly three-fold.
authors.affiliation: Department of Neurosurgery, Center for Aging and Brain Repair, University of South Florida College of Medicine, MDC 78, 12901 Bruce B. Downs Blvd, Tampa 33612, USA. awilling@hsc.usf.edu
authors.forename: Alison E
authors.initials: AE
authors.lastname: Willing
authors.forename: Tanja
authors.initials: T
authors.lastname: Zigova
authors.forename: Melissa
authors.initials: M
authors.lastname: Milliken
authors.forename: Steve
authors.initials: S
authors.lastname: Poulos
authors.forename: Samuel
authors.initials: S
authors.lastname: Saporta
authors.forename: Michael
authors.initials: M
authors.lastname: McGrogan
authors.forename: Gary
authors.initials: G
authors.lastname: Snable
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D008094:Lithium; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D004298:Dopamine