The morphological dynamics of astrocytes are altered in the hippocampus during memory induction. Astrocyte–neuron interactions on synapses are called tripartite synapses. These control the synaptic function in the central nervous system. Astrocytes are activated in a reactive state by STAT3 phosphorylation in 5XFAD mice, an Alzheimer’s disease (AD) animal model. However, changes in astrocyte–neuron interactions in reactive or resting-state astrocytes during memory induction remain to be defined. Here, we investigated the time-dependent changes in astrocyte morphology and the number of astrocyte–neuron interactions in the hippocampus over the course of long-term memory formation in 5XFAD mice. Hippocampal-dependent long-term memory was induced using a contextual fear conditioning test in 5XFAD mice. The number of astrocytic processes increased in both wild-type and 5XFAD mice during memory formation. To assess astrocyte–neuron interactions in the hippocampal dentate gyrus, we counted the colocalization of glial fibrillary acidic protein and postsynaptic density protein 95 via immunofluorescence. Both groups revealed an increase in astrocyte–neuron interactions after memory induction. At 24 h after memory formation, the number of tripartite synapses returned to baseline levels in both groups. However, the total number of astrocyte–neuron interactions was significantly decreased in 5XFAD mice. Administration of Stattic, a STAT3 phosphorylation inhibitor, rescued the number of astrocyte–neuron interactions in 5XFAD mice. In conclusion, we suggest that a decreased number of astrocyte–neuron interactions may underlie memory impairment in the early stages of AD.

中文翻译：

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星形胶质细胞-神经元相互作用的破坏是导致 5XFAD 小鼠学习和记忆障碍的原因：阿尔茨海默病动物模型

在记忆诱导过程中，星形胶质细胞的形态动力学在海马中发生了改变。突触上的星形胶质细胞-神经元相互作用称为三方突触。这些控制中枢神经系统的突触功能。星形胶质细胞在 5XFAD 小鼠（一种阿尔茨海默病 (AD) 动物模型）中通过 STAT3 磷酸化以反应状态被激活。然而，在记忆诱导过程中，反应性或静息状态星形胶质细胞中星形胶质细胞-神经元相互作用的变化仍有待确定。在这里，我们研究了 5XFAD 小鼠在长期记忆形成过程中星形胶质细胞形态的时间依赖性变化和海马中星形胶质细胞-神经元相互作用的数量。在 5XFAD 小鼠中使用情境恐惧条件测试诱导海马依赖性长期记忆。在记忆形成过程中，野生型和 5XFAD 小鼠的星形胶质细胞过程的数量都增加了。为了评估海马齿状回中星形胶质细胞-神经元的相互作用，我们通过免疫荧光计算了胶质纤维酸性蛋白和突触后密度蛋白 95 的共定位。两组都显示在记忆诱导后星形胶质细胞 - 神经元相互作用增加。在记忆形成后 24 小时，两组的三联突触数量恢复到基线水平。然而，星形胶质细胞-神经元相互作用的总数在 5XFAD 小鼠中显着减少。给予 Stattic（一种 STAT3 磷酸化抑制剂）可挽救 5XFAD 小鼠中星形胶质细胞-神经元相互作用的数量。综上所述，