Ganglioside accumulation in activated glia in the developing brain: Comparison between WT and GalNAcT KO mice

Mariko Saito, Gusheng Wu, Maria Hui, Kurt Masiello, Kostantin Dobrenis, Robert W. Ledeen, Mitsuo Saito

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Our previous studies have shown accumulation of GM2 ganglioside during ethanol-induced neurodegeneration in the developing brain, and GM2 elevation has also been reported in other brain injuries and neurodegenerative diseases. Using GM2/GD2 synthase KO mice lacking GM2/GD2 and downstream gangliosides, the current study explored the significance of GM2 elevation in WT mice. Immunohistochemical studies indicated that ethanol-induced acute neurodegeneration in postnatal day 7 (P7) WT mice was associated with GM2 accumulation in the late endosomes/ lysosomes of both phagocytic microglia and increased glial fibrillary acidic protein (GFAP)-positive astrocytes. However, in KO mice, although ethanol induced robust neurodegeneration and accumulation of GD3 and GM3 in the late endosomes/lysosomes of phagocytic microglia, it did not increase the number of GFAP-positive astrocytes, and the accumulation of GD3/GM3 in astrocytes was minimal. Not only ethanol, but also DMSO, induced GM2 elevation in activated microglia and astrocytes along with neurodegeneration in P7 WT mice, while lipopolysaccharide, which did not induce significant neurodegeneration, caused GM2 accumulation mainly in lysosomes of activated astrocytes. Thus, GM2 elevation is associated with activation of microglia and astrocytes in the injured developing brain, and GM2, GD2, or other downstream gangliosides may regulate astroglial responses in ethanol-induced neurodegeneration.

Original languageEnglish (US)
Pages (from-to)1434-1448
Number of pages15
JournalJournal of Lipid Research
Volume56
Issue number8
DOIs
StatePublished - Aug 1 2015

Keywords

  • Activated microglia
  • Astrocyte
  • Brain lipids
  • Ceramide
  • Ethanol
  • GM2/GD2 synthase knockout mice
  • Inflammation
  • Lipopolysaccharide
  • Triglycerides
  • Wild-type mice

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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