Lithium chloride induces the expression of tyrosine hydroxylase in hNT neurons.
In the present study, several doses of lithium chloride were tested for their ability to induce the expression of tyrosine hydroxylase (TH) in neurons derived from a human teratocarcinoma cell line (hNT) after 5 and 10 days in vitro (DIV). Following immunocytochemical staining for tyrosine hydroxylase, the percentage of TH-positive neurons was determined and morphometric analysis, including mean soma profile area and neuritic length, was performed. hNT neurons responded to lithium treatment in a dose-dependent manner. In 5 DIV, the most effective dose of lithium chloride (1.0 mM) increased the number of TH-positive neurons approximately sixfold. In addition, both TH-positive hNT neuron mean soma profile area and neurite length were significantly larger than controls by 60 and 70%, respectively. Moreover, even after withdrawal of lithium chloride on day 5, the number of TH-positive neurons in 10 DIV cultures remained significantly increased. These data suggest that hNT cells are indeed responsive to lithium exposure and may serve as a continual source of TH-expressing neurons in new therapeutic approaches to degenerative brain disease.
Zigova
T
T
Department of Surgery, University of South Florida, Tampa, Florida, 33612, USA.
Willing
A E
AE
Tedesco
E M
EM
Borlongan
C V
CV
Saporta
S
S
Snable
G L
GL
Sanberg
P R
PR
D002454:Cell Differentiation; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018243:Teratocarcinoma / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D014446:Tyrosine 3-Monooxygenase; D018021:Lithium Chloride