Abstract
Niemann–Pick disease type C (NPC) is a progressive neurodegenerative disorder with
characteristic storage of glycolipids in the brain. This study investigated cellular
origin and temporal changes of monosialoganglioside storage in the Balb/c npcnih mouse brain by immunohistochemistry. Anti-GM1 gave positive staining of the hippocampus,
thalamus, cerebellar molecular and Purkinje cell layers in the 3-week old NPC mouse
brain and in general, the staining progressively diminished in an age-dependent manner.
Anti-GM2 gave positive staining of the hippocampus, thalamus, cerebellar granule cell
layer and brainstem nuclei in the 3-week old NPC mouse brain. In contrast to GM1,
GM2 staining in these regions, except for the hippocampus, progressively augmented
in an age-dependent manner. Double labeling experiments with antibodies against glial
fibrillary acidic protein and lysozyme showed localization of GM1 and GM2 in reactive
astrocytes and macrophages, respectively. Thus in the NPC mouse brain, GM1 accumulated
primarily in neurons and astrocytes whereas GM2 accumulated primarily in neurons and
macrophages. Temporal profiles of storage were different from each other and depended
on the cell type, presumably reflecting both developmental changes and progression
of the disease process. We also investigated subcellular sites of storage in primary-cultured
Purkinje cells from the neonatal NPC mouse by immunocytochemistry. In NPC Purkinje
cells, GM1 accumulated both in the cytoplasm and dendrites whereas GM2 showed punctuate
accumulation in perinuclear vesicles. Thus, subcellular sites of storage were also
different between GM1 and GM2 in NPC neurons.
Keywords
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Article info
Publication history
Accepted:
July 18,
2001
Received in revised form:
June 21,
2001
Received:
March 2,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
