Ganglioside GD1 alpha in cerebellar Purkinje cells. Its specific absence in mouse mutants with Purkinje cell abnormality and altered immunoreactivity in response to conjunctive stimuli causing long-term desensitization

Abstract

The alpha-series ganglioside, IV3NeuAc,III6NeuAcGgOse4-Cer(GD1 alpha), was previously identified as a minor constituent in bovine brain gangliosides (Hirabayashi, Y., Hyogo, A., Nakao, T., Tsuchiya, K., Suzuki, Y., Matsumoto, M., Kon, K, and Ando, S. (1990) J. Biol. Chem. 265, 8144-8151). In the present study, we have generated a specific mouse monoclonal antibody against GD1 alpha and explored the distribution of GD1 alpha in murine central nervous system. In adult rat brain, GD1 alpha occurred as a minor constituent, and its expression was exclusively detected in the forebrain, the midbrain and the cerebellum. In the mouse cerebellum, the content of GD1 alpha was reduced significantly in the Purkinje cell-deficient mutants, lurcher (Lc/+), staggerer (sg/sg), and Purkinje cell degeneration (pcd/pcd), but were not reduced in the weaver (wv/wv) mutant, which loses mostly granule cells. The GD1 alpha synthase, assayed in cerebellar microsomes, was also reduced in Purkinje cell-deficient mutants. Immunohistochemistry showed that the staining for GD1 alpha in rat and mouse cerebella was mostly found in the proximal dendrites and cell bodies of Purkinje cells. Also, it appeared slightly in the processes of Bergmann glial cells. The immunoreactivity of GD1 alpha disappeared specifically from the Purkinje cell dendrites and the Bergmann glial processes after co-application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and 8-bromo-guanosine 3':5'-cyclic monophosphate, which induced long-term desensitization of the AMPA-selective glutamate receptors in Purkinje cells. The present data provide suggestive evidence that GD1 alpha ganglioside is enriched in Purkinje cells and may have a role in Purkinje cell functions in the cerebellum.