PROGRESSIVE IMPAIRMENT OF SCHWANN-CELL PROLIFERATION INVITRO IN MURINE GLOBOID-CELL LEUKODYSTROPHY (TWITCHER)

In an attempt to elucidate possible functional derangement in Schwann cells in globoid cell leukodystrophy (GLD), we investigated the proliferative capacity in vitro of Schwann cells from the twitcher (twi/twi), a murine model of human GLD, with thymidine autoradiography and cell counts. Regardless of genotype, Schwann cell numbers increased faster and initial thymidine incorporation was higher in suckling than in adult mice. Compared with cells from heterozygous (+/twi) or normal (+/+) mice, however, proliferative capacity of Schwann cells from twi/twi was depressed in both sucklings and adults. Reflecting in vivo activation secondary to demyelination, the number of labeled Schwann cells was transiently higher during the first 24 h in adult twi/twi cultures but the rate of proliferation declined thereafter and remained low during an 8 day period in culture. Our study demonstrates that proliferative capacity of twi/twi Schwann cells was impaired in vitro, possibly as a comsequence of metabolic perturbation by a deficiency of galactosylceramidase.