Pathologic changes of glial cells in murine model of Niemann–Pick disease type C: Immunohistochemical, lectin-histochemical and ultrastructural observations

BACKGROUND: In recent years, morbid states of glial cells have been reported in several neurodegenerative diseases. We studied neuropathologically the glial cells in a murine model of Niemann-Pick disease type C (NPC) to clarify involvement of glias, the most important supportive cells in the central nervous system, by the disease. METHODS: The brains of sphingomyelinosis mice (spm/spm), aged from 5 to 13 weeks, and 15 of their age-matched normal siblings were studied histopathologically, immunohistochemically and electron micro-scopically. RESULTS: Accumulation of ubiquitin-positive materials was found in the cytoplasm of foam cells and ballooned neurons immunohistochemically. In addition to the morphologically abnormal cells, double immunostaining of ubiquitin and glial fibrillary acidic protein (GFAP) revealed the deposition of ubiquitinated substances in the cytoplasm of astrocytes. Ultrastructurally, numerous concentric lamellar inclusions, so-called 'myelin figures', appeared in the neurons and phagocytotic cells. Some oligodendrocytes also contained 'myelin figure' inclusions and multivesicular inclusions. Astrocytes contained abnormal irregularily-shaped electron dense materials. CONCLUSIONS: In the murine model of NPC, astrocytes and oligodendrocytes are also involved in the morbid processes. Thus, it might be relevant to investigate the glial dysfunction to understand the pathological processes of the disease and to prepare an adjunct therapeutic strategy to manage the patients with NPC.