LITHIUM-CHLORIDE ALTERS CYTOSKELETAL ORGANIZATION IN GROWING, BUT NOT MATURE, CULTURED CHICK SENSORY NEURONS

Biochemical analysis indicates that lithium ion (Li+) has deleterious effects on the metabolism of at least two elements of the cytoskeleton in cultured chick dorsal root ganglia (DRG) neurons. Phosphorylation of newly synthesized middle molecular mass neurofilament polypeptide (NF-M) is inhibited by 10-25 mM LiCl, and tubulin (Tb) synthesized in the presence of Li+ is subject to rapid degradation. These Li+-induced metabolic abnormalities are accompanied by alterations in cellular and cytoskeletal morphology. Treatment of cultures having vigorously growing neurites with 25 mM LiCl results in the cessation of net neurite growth, without causing neurite retraction. Indirect immunofluorescence reveals that in these cultures Li+ provokes an aggregation of NF protein into a dense knot in the cell body/proximal neurite region. The knots contain accumulations of all three NF polypeptides and electron microscopic observation demonstrates that the knots contain intact, but disorganized, filaments. Both the inhibition of neurite outgrowth and NF collapse are reversible. Tubulin and intact microtubules are redistributed in immature cultures treated with Li+ insofar as they are excluded from the NF knots. Neurons in established cultures (e.g., 7 days and beyond) fail to show any difference between Li+ treatment and control conditions in the morphology of the cytoskeletal elements examined.