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.

中文翻译：

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唾液酸化减少引发中年小鼠体内平衡突触和神经元丢失

唾液酸结合 Ig 样凝集素 (Siglec) 受体与神经退行性过程有关，但唾液酸在生理衰老中的作用仍未完全了解。我们研究了唾液酸生物合成所必需的葡萄糖胺-2-差向异构酶/N-乙酰甘露糖胺激酶 (GNE+/-) 杂合小鼠大脑中唾液酸化减少的影响。我们证明 GNE +/- 小鼠在不同的大脑区域具有低唾液酸化，海马中的突触较少，并且在 6 个月时已经减少了小胶质细胞分支，随后在 12 个月时神经元丢失增加。转录组学分析显示没有促炎变化，表明先天稳态免疫过程导致 GNE+/- 小鼠衰老过程中突触和神经元的去除。与补体 C3 缺陷小鼠杂交挽救了较早发生的神经元和突触损失以及小胶质细胞分支的变化。因此，糖萼的唾液酸有助于大脑稳态，并作为大脑先天免疫系统的识别系统。