Reference : Reduced sialylation triggers homeostatic synapse and neuronal loss in middle-aged mice
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/42465
Reduced sialylation triggers homeostatic synapse and neuronal loss in middle-aged mice
English
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 mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Gérard, Deborah [University of Luxembourg, Belvaux, Luxembourg > Life Sciences Research Unit]
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 mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Sinkkonen, Lasse mailto [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]
2020
Neurobiology of Aging
Elsevier
Yes (verified by ORBilu)
International
0197-4580
1558-1497
New York
Netherlands
[en] Microglia ; neuroinflammation ; sialic acid ; aging ; neurodegeneration ; glycocalyx
[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.
Deutsche For-schungsgemeinschaf, Innovative Medicines Initiative 2 Joint Undertaking, Boehringer IngelheimFonds
Researchers ; Professionals
http://hdl.handle.net/10993/42465
10.1016/j.neurobiolaging.2020.01.008

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