Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat.
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.
Willing
Alison E
AE
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
Zigova
Tanja
T
Milliken
Melissa
M
Poulos
Steve
S
Saporta
Samuel
S
McGrogan
Michael
M
Snable
Gary
G
Sanberg
Paul R
PR
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
D008094:Lithium; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D004298:Dopamine