title: Bi-phasic gliosis drives neuropathology in a Sandhoff disease mouse model.
abstract: Microgliosis and astrogliosis are known to be exacerbating factors in the progression of the lysosomal storage disorder Sandhoff disease. We have also found evidence for excitotoxicity via glutamate receptors in Sandhoff disease. To view the interaction of these cascades, we measured cerebellar expression of markers for gliosis, apoptosis, and excitatory synapses over the disease course in a Sandhoff disease mouse model. We observe a 2-stage model, with initial activation of microgliosis as early as 60days of age, followed by a later onset of astrogliosis, caspase-mediated apoptosis, and reduction in GluR1 at approximately 100days of age. These results implicate immune cells as first responders in Sandhoff disease.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ont. L8S 4K1, Canada. Electronic address: hooperaw@Mcmaster.ca.
authors.forename: Alexander W M
authors.initials: AW
authors.lastname: Hooper
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ont. L8S 4K1, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont. L8S 4L8, Canada. Electronic address: igdoura@Mcmaster.ca.
authors.forename: Suleiman A
authors.initials: SA
authors.lastname: Igdoura
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012497:Sandhoff Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054821:beta-Hexosaminidase beta Chain / Q000235:genetics
chemical_list: C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain
keywords: Apoptosis; Astrogliosis; Cleaved-caspase 9; Glur1; Microgliosis; Sandhoff disease