[en] Sialic acid-binding receptors (Siglecs) are linked to neurodegenerative processes, but the role of sialic acids in physiological aging is still not fully understood. We investigated the impact of reduced sialylation in the brain of mice heterozygous for the enzyme glucosamine-2-epimerase/N-acetylmannosamine kinase (GNE+/-) that is essential for sialic acid biosynthesis. We demonstrate that GNE+/- mice have hyposialylation in different brain regions, less synapses in the hippocampus and reduced microglial arborization already at 6 months followed by increased loss of neurons at 12 months. A transcriptomic analysis revealed no pro-inflammatory changes indicating an innate homeostatic immune process leading to the removal of synapses and neurons in GNE+/- mice during aging. Crossbreeding with complement C3-deficient mice rescued the earlier onset of neuronal and synaptic loss as well as the changes in microglial arborization. Thus, sialic acids of the glycocalyx contribute to brain homeostasis and act as a recognition system for the innate immune system in the brain.
Centre de recherche :
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Biochimie, biophysique & biologie moléculaire
Auteur, co-auteur :
Klaus, Christine; Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, Germany > Neural Regeneration
Hansen, Jan N.; Institute of Innate Immunity, University Hospital of Bonn, Germany > Biophysical Imaging
GINOLHAC, Aurélien ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
GERARD, Déborah ; University of Luxembourg ; Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Fondation Recherche sur le Cancer et les Maladies du Sang, Pavillon 2, 6A rue Barblé, L-1210, Luxembourg, Luxembourg
Gnanapragassam, Vinayaga S.; Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
Horstkorte, Rüdiger; Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
Rossdam, Charlotte; Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
Buettner, Falk F. R.; Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany
SAUTER, Thomas ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
SINKKONEN, Lasse ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Neumann, Harald; Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, Germany > Neural Regeneration
Linnartz-Gerlach, Bettina; Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, Germany > Neural Regeneration
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Reduced sialylation triggers homeostatic synapse and neuronal loss in middle-aged mice
Date de publication/diffusion :
2020
Titre du périodique :
Neurobiology of Aging
ISSN :
0197-4580
eISSN :
1558-1497
Maison d'édition :
Elsevier, New York, Pays-Bas
Peer reviewed :
Peer reviewed vérifié par ORBi
Focus Area :
Systems Biomedicine
Organisme subsidiant :
Deutsche For-schungsgemeinschaf, Innovative Medicines Initiative 2 Joint Undertaking, Boehringer IngelheimFonds
