title: Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice.
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.
authors.affiliation: Divisions of Neurochemistry Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016.
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Neurology and Neurosciences, Rutgers-New Jersey Medical School, Newark, NJ 07103.
authors.forename: Gusheng
authors.initials: G
authors.lastname: Wu
authors.affiliation: Divisions of Neurochemistry Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962.
authors.forename: Maria
authors.initials: M
authors.lastname: Hui
authors.affiliation: Divisions of Neurochemistry Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962.
authors.forename: Kurt
authors.initials: K
authors.lastname: Masiello
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461.
authors.forename: Kostantin
authors.initials: K
authors.lastname: Dobrenis
authors.affiliation: Department of Neurology and Neurosciences, Rutgers-New Jersey Medical School, Newark, NJ 07103.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ledeen
authors.affiliation: Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016 Analytical Psychopharmacology, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000254:growth & development*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism*; D055786:Gene Knockout Techniques; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000172:deficiency* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D004121:Dimethyl Sulfoxide; D000431:Ethanol; D005732:Gangliosides; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D017350:N-Acetylgalactosaminyltransferases; D009419:Nerve Tissue Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C528900:glial fibrillary astrocytic protein, mouse
keywords: GM2/GD2 synthase knockout mice; activated microglia; astrocyte; brain lipids; ceramide; ethanol; inflammation; lipopolysaccharide; triglycerides; wild-type mice