Progressive neuronal loss in the ventral posterior lateral and medial nuclei of thalamus in Niemann-Pick disease type C mouse brain

Niemann-Pick disease type C (NP-C) disease is a progressive and fatal neuro logical disorder characterized by accumulation of cholesterol and glycosphi ngolipids in peripheral tissues and that of glycosphingolipids in the brain . A C57BL/KsJ-npc1(spm) mutant strain is a genetically authentic model of N P-C. This study investigated neuronal cell loss and lipid accumulation in t he npc1(spm) 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 c ell 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 acc umulation of cholesterol was detectable in most of the large neurons by fil ipin staining in the brain of homozygous mice. In contrast to the diffuse s taining pattern in normal brains, the neuropils of the neurons in the brain of homozygous mice were stained in a punctate pattern. The ubiquitous accu mulation 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. (C) 2001 Elsevier Science B.V. All rights reserved.