PROLIFERATIVE CAPACITY OF OLIGODENDROCYTES IN THE DEMYELINATING TWITCHER SPINAL-CORD

The proliferative capacity of oligodendrocytes was investigated in the spinal white matter of the twitcher mouse, a murine model of a geneti c demyelinating disease globoid cell leukodystrophy (GLD), in which de generation of oligodendrocytes due to metabolic perturbation has been well documented. In normal mice at 30 and 45 days of age, proliferatin g cells labeled with 5-bromo-2'-deoxyuridine (BrdU) were scarce, and t he majority of BrdU-labeled cells did not immunostain with antibodies for oligodendrocytes, astrocytes, or microglia/macrophages. Only a few cells with markers for oligodendrocytes, carbonic anhydrase (CA), or the Pi form of glutathione-S-transferase (Pi), were labeled with BrdU. In the twitcher spinal cord, total numbers of BrdU-labeled cells were almost 6 times that of the normal littermate mice at 30 days of age, and 28 times at 45 days of age. However, this increase was largely due to an increase of cells labeled with F4/80, a marker for the microgli a/macrophages. CA or Pi positive cells only constituted less than 10% of all labeled cells. With progression of demyelination from 30-45 day s, total numbers of CA positive or Pi positive oligodendrocytes decrea sed, but percentages of cells double-labeled with BrdU and CA or Pi re mained fairly constant. The results indicated that oligodendrocytes pr oliferated, to some extent, in the twitcher despite the genetic metabo lic defect, and their decrease in number with progression of disease w as not due to declined proliferation but rather cellular degeneration as the result of an intrinsic metabolic perturbation. (C) 1995 Wiley-L iss, Inc.