Sites and temporal changes of gangliosides GM1/GM2 storage in the Niemann-Pick disease type C mouse brain

Niemann-Pick disease type C (NPC) is, a progressive neurodegenerative disor der with characteristic storage of glycolipids in the brain. This study inv estigated cellular origin and temporal changes, of monosialoganglioside sto rage in the Balb/c npc(nih) mouse brain by immunohistochemistry. Anti-GM1 g ave positive staining of the hippocampus, thalamus, cerebellar molecular an d Purkinje cell layers in the 3-week old NPC mouse brain and in general, th e staining progressively diminished in an age-dependent manner. Anti-GM2 ga ve positive staining of the hippocampus, thalamus, cerebellar granule cell layer and brainstem nuclei in the 3-week old NPC mouse brain. In contrast t o GM1, GM2 staining in these regions, except for the hippocampus, progressi vely augmented in an age-dependent manner. Double labeling experiments with antibodies against glial fibrillary acidic protein and lysozyme showed loc alization of GM1 and GM2 in reactive astrocytes and macrophages, respective ly. Thus in the NPC mouse brain, GM1 accumulated primarily in neurons and a strocytes whereas GM2 accumulated primarily in neurons and macrophages. Tem poral profiles of storage were different from each other and depended on th e cell type, presumably reflecting both developmental changes and progressi on of the disease process. We also investigated subcellular sites of storag e in primary-cultured Purkinje cells from the neonatal NPC mouse by immunoc ytochemistry. In NPC Purkinje cells, GM1 accumulated both in the cytoplasm and dendrites whereas GM2 showed punctuate accumulation in perinuclear vesi cles. Thus, subcellular sites of storage were also different between GM1 an d GM2 in NPC neurons. (C) 2001 Elsevier Science B.V. All rights reserved.