Differential Cellular Enrichment of Gangliosides in the Mouse Cerebellum: Analysis Using Neurological Mutants

Thomas N. Seyfried, Robert K. Yu, Nobuko Miyazawa

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Abstract

Abstract: The cellular distribution of gangliosides in the cerebellum was studied in a series of adult mouse mutants that lose specific populations of neurons. The weaver (wv) mutation destroys the vast majority of granule cells, whereas the Purkinje cell degeneration mutation (pcd) destroys the vast majority of Purkinje cells. The staggerer (sg) and lurcher (Lc) mutations, on the other hand, destroy the vast majority of both granule and Purkinje cells. A proliferation of reactive glial cells, which occurs as a consequence of neuronal loss, has been reported in the sg/sg and pcd/pcd mutants, but not in the wv/wv mutant. Compared with the normal (+/+) mice, the concentration (μg/100 mg dry weight) of GD1a was significantly reduced in those mutants that lost granule cells, but was not reduced in the pcd/pcd mutant. The concentration of GTIa, on the other hand, was significantly reduced in those mutants that lost Purkinje cells, but was not reduced in the wv/wv mutant. A significant elevation in the concentration of GD3, which may be related to the proliferation of reactive glial cells, was observed in the pcd/pcd, sglsg, and Lc/+ mutants, but was not observed in the wv/wv mutant. Because these ganglioside abnormalities were confined to the cerebellum, they cannot result from genetic defects in ganglioside metabolism. Instead, these abnormalities result from a differential enrichment of gangliosides in neural membranes. Our findings suggest that GDT1a is more heavily concentrated in granule cells than Purkinje cells, whereas the opposite appears true for GTla. It also appears that GD3 is enriched in reactive glial cells and may play an important role during the morphological transformation of neural membranes.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalJournal of Neurochemistry
Volume38
Issue number2
DOIs
Publication statusPublished - Feb 1982
Externally publishedYes

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Keywords

  • Cerebellum
  • Gangliosides
  • Gliosis
  • Granule cells
  • Mutant mice
  • Purkinje cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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