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Reduced sialylation triggers homeostatic synapse and neuronal loss in middle-aged mice.
Klaus, Christine; Hansen, Jan N; Ginolhac, Aurélien; Gérard, Deborah; Gnanapragassam, Vinayaga S; Horstkorte, Rüdiger; Rossdam, Charlotte; Buettner, Falk F R; Sauter, Thomas; Sinkkonen, Lasse; Neumann, Harald; Linnartz-Gerlach, Bettina.
Afiliación
  • Klaus C; Neural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, Germany.
  • Hansen JN; Biophysical Imaging, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
  • Ginolhac A; Epigenetics Team, Systems Biology Group, Life Sciences Research Unit, University of Luxembourg, Belvaux, Luxembourg.
  • Gérard D; Epigenetics Team, Systems Biology Group, Life Sciences Research Unit, University of Luxembourg, Belvaux, Luxembourg.
  • Gnanapragassam VS; Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
  • Horstkorte R; Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
  • Rossdam C; Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
  • Buettner FFR; Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
  • Sauter T; Epigenetics Team, Systems Biology Group, Life Sciences Research Unit, University of Luxembourg, Belvaux, Luxembourg.
  • Sinkkonen L; Epigenetics Team, Systems Biology Group, Life Sciences Research Unit, University of Luxembourg, Belvaux, Luxembourg.
  • Neumann H; Neural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, Germany. Electronic address: harald.neumann@uni-bonn.de.
  • Linnartz-Gerlach B; Neural Regeneration, Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, Germany.
Neurobiol Aging ; 88: 91-107, 2020 04.
Article en En | MEDLINE | ID: mdl-32087947
Sialic acid-binding Ig-like lectin (Siglec) receptors 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Siálicos / Sinapsis / Envejecimiento / Neuronas Límite: Animals Idioma: En Revista: Neurobiol Aging Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Siálicos / Sinapsis / Envejecimiento / Neuronas Límite: Animals Idioma: En Revista: Neurobiol Aging Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos