Reduced sialylation triggers complement c3-mediated neuronal loss in aging mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB31769 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3233422.fastq.gz | Fastqsanger.gz | |||
| ERR3233423.fastq.gz | Fastqsanger.gz | |||
| ERR3233424.fastq.gz | Fastqsanger.gz | |||
| ERR3233425.fastq.gz | Fastqsanger.gz | |||
| ERR3233426.fastq.gz | Fastqsanger.gz |
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Project 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.
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Project description:Reduced sialylation triggers complement c3-mediated neuronal loss in aging mice
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