Ganglioside G sub(D1 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

• Published in: The Journal of biological chemistry 1994-01, Vol.269 (51), p.32418-32425
• Main Authors: Furuya, S, Irie, F, Hashikawa, T, Nakazawa, K, Kozakai, A, Hasegawa, A, Sudo, K, Hirabayashi, Y
• Format: Article
• Language: English
• ISSN: 0021-9258

The alpha -series ganglioside, IV super(3)NeuAc,III super(6)NeuAcGgOse sub(4)-Cer (G sub(D1 alpha )), was previously identified as a minor constituent in bovine brain gangliosides. In the present study, we have generated a specific mouse monoclonal antibody against G sub(D1 alpha ) and explored the distribution of G sub(D1 alpha ) in murine central nervous system. In adult rat brain, G sub(D1 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 G sub(D1 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 G sub(D1 alpha ) synthase, assayed in cerebellar microsomes, was also reduced in Purkinje cell-deficient mutants. Immunohistochemistry showed that the staining for G sub(D1 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 G sub(D1 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-bromoguanosine 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 sub(D1 alpha ) ganglioside is enriched in Purkinje cells and may have a role in Purkinje cell functions in the cerebellum.