title: Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain.
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.
authors.affiliation: Division of Analytical Psychopharmacology, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Saito
authors.forename: Goutam
authors.initials: G
authors.lastname: Chakraborty
authors.forename: Relish
authors.initials: R
authors.lastname: Shah
authors.forename: Rui-Fen
authors.initials: RF
authors.lastname: Mao
authors.forename: Asok
authors.initials: A
authors.lastname: Kumar
authors.forename: Dun-Sheng
authors.initials: DS
authors.lastname: Yang
authors.forename: Kostantin
authors.initials: K
authors.lastname: Dobrenis
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development* / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005678:G(M2) Ganglioside / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D005678:G(M2) Ganglioside; D000431:Ethanol; D045304:Cytochromes c; D053148:Caspase 3