Abstract
Niemann–Pick disease type C (NP-C) disease is a progressive and fatal neurological
disorder characterized by accumulation of cholesterol and glycosphingolipids in peripheral
tissues and that of glycosphingolipids in the brain. A C57BL/KsJ-npc1spm mutant strain is a genetically authentic model of NP-C. This study investigated neuronal
cell loss and lipid accumulation in the npc1spm mouse brain. Nissl-staining revealed abundant swollen neurons in the neocortex, piriform
cortex, hippocampus and basal ganglia at 3–4 wk of age. In addition to loss of the
Purkinje cells, we found a conspicuous cell loss in the ventral posterial lateral
(VPL) and medial (VPM) nuclei of thalamus, which became apparent after 4–5 wk. Biochemical
analyses revealed no increase of cholesterol in the lipid extracts whereas a substantial
accumulation of cholesterol was detectable in most of the large neurons by filipin
staining in the brain of homozygous mice. In contrast to the diffuse staining pattern
in normal brains, the neuropils of the neurons in the brain of homozygous mice were
stained in a punctate pattern. The ubiquitous accumulation excludes a direct role
of cholesterol in the progressive neuronal loss in the Purkinje cell layer and in
the VPL and VPM of the thalamus.
Keywords
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Article info
Publication history
Accepted:
March 24,
2001
Received in revised form:
February 12,
2001
Received:
September 25,
2000
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
