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Essential Roles of Gangliosides in the Formation and Maintenance of Membrane Microdomains in Brain Tissues

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Abstract

Gangliosides are considered to be involved in the maintenance and repair of nervous tissues. Recently, novel roles of gangliosides in the regulation of complement system were reported. Here we summarized roles of gangliosides in the formation and maintenance of membrane microdomains in brain tissues by comparing complement activation, inflammatory reaction and disruption of glycolipid-enriched microdomain (GEM)/rafts among several mutant mice of ganglioside synthases. Depending on the defects in ganglioside compositions, corresponding up-regulation of complement-related genes, proliferation of astrocytes and infiltration of microglia were found with gradual severity. Immunoblotting of fractions separated by sucrose density gradient ultracentrifugation revealed that DAF and NCAM having GPI-anchors tended to disappear from the raft fraction with intensities of DKO > GM2/GD2 synthase KO > GD3 synthase KO > WT. The lipid raft markers tended to disperse from the raft fractions with similar intensities. Phospholipids and cholesterol also tended to decrease in GEM/rafts in GM2/GD2 synthase KO and DKO, although total amounts were almost equivalent. All these results indicate that GEM/rafts architecture is destroyed by ganglioside deficiency with gradual intensity depending on the degree of defects of their compositions. Implication of inflammation caused by deficiency of gangliosides in various neurodegenerative diseases was discussed.

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Authors and Affiliations

  1. Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan

    Yuhsuke Ohmi, Yuki Ohkawa, Yoshio Yamauchi, Orie Tajima, Keiko Furukawa & Koichi Furukawa

  2. Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai, 487-8501, Japan

    Orie Tajima & Keiko Furukawa

Authors
  1. Yuhsuke Ohmi
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  2. Yuki Ohkawa
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  3. Yoshio Yamauchi
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  4. Orie Tajima
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  5. Keiko Furukawa
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  6. Koichi Furukawa
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Correspondence to Koichi Furukawa.

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Special issue: In Honour of Bob Leeden.

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Ohmi, Y., Ohkawa, Y., Yamauchi, Y. et al. Essential Roles of Gangliosides in the Formation and Maintenance of Membrane Microdomains in Brain Tissues. Neurochem Res 37, 1185–1191 (2012). https://doi.org/10.1007/s11064-012-0764-7

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  • DOI: https://doi.org/10.1007/s11064-012-0764-7

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