Ganglioside G(D1α) in cerebellar Purkinje cells: Its specific absence in mouse mutants with Purkinje cell abnormality and altered immunoreactivity in response tc conjunctive stimuli causing long term desensitization

S. Furuya, F. Irie, T. Hashikawa, K. Nakazawa, A. Kozakai, A. Hasegawa, K. Sudo, Y. Hirabayashi

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Abstract

The α-series ganglioside, IV3NeuAc,III6NeuAcGgOse4Cer (G(D1α)), 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, 81448151). In the present study, we have generated a specific mouse monoclonal antibody against G(D1α) and explored the distribution of G(D1α) in murine central nervous system. In adult rat brain, G(D1α) 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 G(D1α) 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 G(D1α) synthase, assayed in cerebellar microsomes, was also reduced in Purkinje cell-deficient mutants. Immunohistochemistry showed that the staining for G(D1α) 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 G(D1α) disappeared specifically from the Purkinje cell dendrites and the Bergmann glial processes after co-application of α-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 G(D1α) ganglioside is enriched in Purkinje cells and may have a role in Purkinje cell functions in the cerebellum.

Original languageEnglish
Pages (from-to)32418-32425
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number51
Publication statusPublished - 1994

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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