1. Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain.
- Author
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Saito M, Chakraborty G, Shah R, Mao RF, Kumar A, Yang DS, Dobrenis K, and Saito M
- Subjects
- Animals, Blotting, Western, Brain pathology, Brain Chemistry drug effects, Caspase 3 metabolism, Cytochromes c metabolism, Endosomes drug effects, Endosomes metabolism, Enzyme Activation physiology, Immunohistochemistry, Lysosomes drug effects, Lysosomes metabolism, Mice, Mice, Inbred C57BL, Microscopy, Electron, Mitochondria metabolism, Nerve Degeneration pathology, Subcellular Fractions drug effects, Subcellular Fractions metabolism, Apoptosis drug effects, Brain growth & development, Central Nervous System Depressants pharmacology, Ethanol pharmacology, G(M2) Ganglioside biosynthesis, Nerve Degeneration metabolism
- 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 non-synaptic mitochondrial fractions as well as in a lysosome-enriched 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., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)
- Published
- 2012
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