title: Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation.
abstract: This study evaluated whether GM(2) ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing β-hexosaminidase rescue experiments in neurons of HexB(-/-) mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of HexB(-/-) mice by the Thy1 promoter. Despite β-hexosaminidase restoration in neurons was sufficient in rescuing HexB(-/-) mice from GM(2) neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM(2) presence in this cell type. In conclusion, our results suggest that neuroinflammation is not sufficient to elicit neurodegeneration as long as neuronal function is restored.
authors.affiliation: Department of Children's Dentistry, Stony Brook University, Stony Brook, NY 11894-8701, USA. kyrkanides@gmail.com
authors.forename: Stephanos
authors.initials: S
authors.lastname: Kyrkanides
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Brouxhon
authors.forename: Ross H
authors.initials: RH
authors.lastname: Tallents
authors.forename: Jen-nie H
authors.initials: JN
authors.lastname: Miller
authors.forename: John A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D012497:Sandhoff Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001619:beta-N-Acetylhexosaminidases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D001619:beta-N-Acetylhexosaminidases