Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain

Mitsuo Saito, Goutam Chakraborty, Relish Shah, Rui Fen Mao, Asok Kumar, Dun Sheng Yang, Kostantin Dobrenis, Mariko Saito

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic neurodegeneration in 7-day-old mice. A small but a significant increase observed 2 h after ethanol exposure was followed by a marked increase around 24 h. Subcellular fractionation of the brain 24 h after ethanol treatment indicated that GM2 increased in synaptic and nonsynaptic mitochondrial fractions as well as in a lysosomeenriched fraction characteristic to the ethanol-exposed brain. Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong punctate staining mainly in activated microglia, in which it partially overlapped with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was weaker neuronal staining, which partially co-localized with complex IV, a mitochondrial marker, and was augmented in cleaved caspase 3-positive neurons. In contrast, the control brain showed only faint and diffuse GM2 staining in neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced cytochrome c release in a manner similar to that of GD3 ganglioside. Because ethanol is known to trigger mitochondria- mediated apoptosis with cytochrome c release and caspase 3 activation in the 7-day-old mouse brain, the GM2 elevation in mitochondria may be relevant to neuroapoptosis. Subsequently, activated microglia accumulated GM2, indicating a close relationship between GM2 and ethanol-induced neurodegeneration.

Original languageEnglish (US)
Pages (from-to)649-661
Number of pages13
JournalJournal of Neurochemistry
Volume121
Issue number4
DOIs
StatePublished - May 1 2012

Keywords

  • Activated microglia
  • Apoptotic neurodegeneration
  • Ethanol
  • GM2 ganglioside
  • Lysosome
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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