Effect of purkinje cell loss on cerebellar gangliosides in nervous mutant mice

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Abstract
The distribution of cerebellar gangliosides was studied in adult (73 ± 2 days) nervous (nr/nr) mutant mice which lose 50–90% of their Purkinje cells. This neuronal loss is associated with significant reductions in cerebellar weight and ganglioside concentration. The cerebellar dry weights (mg) and the ganglioside concentrations (μg N‐acetylneuraminic acid per 100 mg dry weight) in nr/nr mice and age‐matched normal littermates (+/?) are 7.4 ± 0.3 mg and 13.2 ± 0.4 mg; and 411.7 ± 4.8 μg and 438.5 ± 2.1 μg, respectively. Abnormalities were also observed for the concentration of certain ganglioside species. Most notably, GT1a is significantly reduced by 42%, and GD3 is significantly increased by 29% in the nr/nr mice compared to the +/? mice. The nr/nr mice also express a slight but significant reduction in GT1b. No ganglioside abnormalities were observed between the nr/nr and +/? mice in cerebral cortex. We previously found reduced cerebellar GT1a content in other mutants that also lose Purkinje cells, i.e., sg/sg, pcd/pcd, and Lc/+. GT1a is not reduced, however, in wv/wv mice that lose mostly granule cells. The findings in nr/nr mice are therefore consistent with our hypothesis that GT1a is enriched in Purkinje cells. GD1a, which is enriched in mature granule cells, is not reduced in the nr/nr mice. Since we previously found that GD3 is a good marker for reactive glia in neurological disease, the elevated GD3 concentration in the nr/nr mice indicates a mild gliosis. Our findings with nr/nr and the other neurological mutants indicate that gangliosides can be useful as cell‐surface markers for monitoring changes in the cytoarchitecture of the mouse cerebellum.