当前位置: X-MOL 学术Nat. Metab. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model
Nature Metabolism ( IF 18.9 ) Pub Date : 2025-01-24 , DOI: 10.1038/s42255-024-01189-3
Yasmine Rabah, Jean-Paul Berwick, Nisrine Sagar, Laure Pasquer, Pierre-Yves Plaçais, Thomas Preat

Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron H2O2 signalling cascade in Drosophila that is essential for long-term memory formation. Stimulation of astrocytes by acetylcholine induces an increase in intracellular calcium ions, which triggers the generation of extracellular superoxide (O2) by astrocytic NADPH oxidase. Astrocyte-secreted superoxide dismutase 3 (Sod3) converts O2 to hydrogen peroxide (H2O2), which is imported into neurons of the olfactory memory centre, the mushroom body, as revealed by in vivo H2O2 imaging. Notably, Sod3 activity requires copper ions, which are supplied by neuronal amyloid precursor protein. We also find that human amyloid-β peptide, implicated in Alzheimer’s disease, inhibits the nAChRα7 astrocytic cholinergic receptor and impairs memory formation by preventing H2O2 synthesis. These findings may have important implications for understanding the aetiology of Alzheimer’s disease.



中文翻译:


星形胶质细胞到神经元的 H2O2 信号转导支持果蝇的长期记忆形成,但在阿尔茨海默病模型中受损



星形胶质细胞有助于保护神经元免受活性氧 (ROS) 造成的潜在损伤。虽然 ROS 也可以发挥有益的作用,但目前尚不清楚神经元 ROS 信号在记忆形成过程中是如何被激活的,以及星形胶质细胞是否在此过程中发挥作用。在这里,我们在果蝇中发现了星形胶质细胞到神经元的 H2O2 信号级联反应,这对长期记忆的形成至关重要。乙酰胆碱刺激星形胶质细胞诱导细胞内钙离子的增加,从而触发星形胶质细胞 NADPH 氧化酶产生细胞外超氧化物 (O2)。星形胶质细胞分泌的超氧化物歧化酶 3 (Sod3) 将 O2 转化为过氧化氢 (H2O2),过氧化氢被输入嗅觉记忆中枢(蘑菇体)的神经元,如体内 H2O2 成像所示。值得注意的是,Sod3 活性需要铜离子,铜离子由神经元淀粉样蛋白前体蛋白提供。我们还发现,与阿尔茨海默病有关的人淀粉样蛋白β肽抑制 nAChRα7 星形胶质细胞胆碱能受体,并通过阻止 H2O2 合成来损害记忆形成。这些发现可能对理解阿尔茨海默病的病因具有重要意义。

更新日期:2025-01-24
down
wechat
bug