Degeneration of neurons and glia in the Niemann-Pick C mouse is unrelated to the low-density lipoprotein receptor

The BALB/c mouse model of Niemann-Pick type C disease exhibits similar neur opathological features to the human condition, including cerebral atrophy, demyelination of the corpus callosum, and degeneration of cerebellar Purkin je cells. The gene defect in Niemann-Pick C disease causes cholesterol to a ccumulate within the lysosomal compartment of neurons and glial cells. In o rder to determine whether cholesterol accumulation through the low-density lipoprotein receptor pathway plays an important role in the degenerative pr ocess, Niemann-Pick C mice were crossed with low-density lipoprotein recept or knockout mice. The purpose of the present study was to determine whether degeneration of neurons and glial cells is reduced in Niemann-Pick C anima ls lacking the low-density lipoprotein receptor. Using stereological counti ng methods, Purkinje cells were counted in the cerebellum and glial cell bo dies were counted in the corpus callosum in mice at 3, 7.5 and 11 weeks of age. In the Niemann-Pick C animals, compared to wild-type control mice, the re were 48% fewer glial cells at 3 weeks of age, and by I I weeks of age th ere were 63% fewer glial cells. Purkinje cells were decreased in number by 13% at 3 weeks of age, and by 11 weeks of age there was a 96% loss. In the Niemann-Pick C animals lacking low-density lipoprotein receptors, there was no difference in the magnitude of glial cell or Purkinje cell loss compare d to the Niemann-Pick C animals. These data indicate that both neurons and.-lia are vulnerable to degenerati on in the Niemann-Pick C mouse, but that blocking the accumulation of chole sterol through the low-density lipoprotein receptor pathway does not alter the degenerative phenotype of Niemann-Pick C disease. (C) 2001 IBRO. Publis hed by Elsevier Science Ltd. All rights reserved.