In the present study, several doses of lithium chloride were tested for the
ir ability to induce the expression of tyrosine hydroxylase (TH) in neurons
derived from a human teratocarcinoma cell line (hNT) after 5 and 10 days i
n vitro (DIV). Following immunocytochemical staining for tyrosine hydroxyla
se, the percentage of TH-positive neurons was determined and morphometric a
nalysis, including mean soma profile area and neuritic length, was performe
d. hNT neurons responded to lithium treatment in a dose-dependent manner. I
n 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 signific
antly larger than controls by 60 and 70%, respectively. Moreover, even afte
r withdrawal of lithium chloride on day 5, the number of TH-positive neuron
s in 10 DIV cultures remained significantly increased. These data suggest t
hat 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. (C) 1999 Academic Press.