| Experiment Id | E-MTAB-7790 | Name | Reduced sialylation triggers complement c3-mediated neuronal loss in ageing mice |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | ArrayExpress | Curation Date | 2020-06-15 |
| description | Mice heterozygous for the bifunctional enzyme glucosamine-2-epimerase/N-acetylmannosamine kinase (GNE+/-), which is essential for sialic acid biosynthesis, showed reduced gne transcription and sialylation in different brain regions. We found synapse loss in the hippocampus of GNE+/- mice at 6 months followed by a gradual loss of neurons in the hippocampus and substantia nigra at 12 months. Moreover, GNE+/- mice showed reduced arborization of microglia already at 6 months. A transcriptomic analysis revealed only minor inflammatory changes with slightly increased Interleukin 1β levels, indicating a homeostatic removal of synapses and neurons. Crossbreeding with complement component 3-deficient mice rescued the early onset loss of neurons and synapses in the GNE+/- mice. Thus, an intact sialic acid covered glycocalyx plays an essential role in maintaining brain homeostasis. Even a minor reduction in the sialic acid level leads to reduced microglial arborization and complement-mediated loss of neurons and synapses. |
