early neurodegeneration progresses independently of microglial activation by heparan sulfate in the brain of mucopolysaccharidosis iiib mice神经退行性变的早期发展独立的小胶质激活大脑中的硫酸乙酰肝素的黏多糖病希望老鼠.pdfVIP

Early Neurodegeneration Progresses Independently of Microglial Activation by Heparan Sulfate in the Brain of Mucopolysaccharidosis IIIB Mice ´ ˆ 1 1 ´ 2 1 ´ 1 Jerome Ausseil , Nathalie Desmaris , Stephanie Bigou , Ruben Attali , Sebastien Corbineau , Sandrine 1 1 3 4 ` 3 ´ ` 5 Vitry , Mathieu Parent , David Cheillan , Maria Fuller , Irene Maire , Marie-Therese Vanier , Jean-Michel Heard1* ´ ´ ´ ´ ´ ˆ ˆ 1 Unite Retrovirus et Transfert Genetique, INSERM U622, Department of Neuroscience, Institut Pasteur, Paris, France, 2 Service de Neurologie Pediatrique, Hopital Bicetre, ˆ ˆ Assistance Publique/Hopitaux de Paris, INSERM U802, 94000, le Kremlin-Bicetre, France, 3 Groupement hospitalier est, CBPE, Bron, France, 4 Genetic Medicine, Children, ¨ ´ ´ ¨ Youth and Women’s Health Service, North Adelaıde, Australia, 5 INSERM U820, Faculte de Medecine Laennec, Lyon, France Abstract Background: In mucopolysaccharidosis type IIIB, a lysosomal storage disease causing early onset mental retardation in children, the production of abnormal oligosaccharidic fragments of heparan sulfate is associated with severe neuropathology and chronic brain inflammation. We addressed causative links between the biochemical,