美国弗吉尼亚大学医学院Harald Sontheimer团队近期取得重要工作进展，他们研究提出，小鼠星形胶质细胞需要神经元周围网（PNN）维持突触稳态。相关研究成果2024年7月17日在线发表于《自然—神经科学》杂志上。

据介绍，PNN是紧密包裹快速发放抑制性神经元细胞体的细胞外基质。PNN稳定突触并抑制突触可塑性。

研究人员发现，快速发放中间神经元的突触终端定位于成年小鼠体感皮层中PNN的孔中。大约95%的PNN孔中包含表达Kir4.1、谷氨酸和GABA转运蛋白的突触和星形胶质细胞过程。因此，PNN的孔包含三重突触。在成年小鼠大脑中，PNN的降解导致神经元胞体的星形胶质细胞覆盖范围扩大，但不改变轴突末端。PNN的丧失会损害星形胶质细胞对神经递质和钾离子的摄取，导致谷氨酸溢出到突触外空间。

总之，这一研究表明，在生理条件下，PNN和星形胶质细胞协同作用以控制突触信号的释放。在阿尔茨海默病和癫痫的小鼠模型中，PNN被破坏，这种协同作用也发生了改变。

附：英文原文

Title: Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice

Author: Tewari, Bhanu P., Woo, AnnaLin M., Prim, Courtney E., Chaunsali, Lata, Patel, Dipan C., Kimbrough, Ian F., Engel, Kaliroi, Browning, Jack L., Campbell, Susan L., Sontheimer, Harald

Issue&Volume: 2024-07-17

Abstract: Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex. Approximately 95% of holes in the PNNs contain synapses and astrocytic processes expressing Kir4.1, glutamate and GABA transporters. Hence, holes in the PNNs contain tripartite synapses. In the adult mouse brain, PNN degradation causes an expanded astrocytic coverage of the neuronal somata without altering the axon terminals. The loss of PNNs impairs astrocytic transmitter and potassium uptake, resulting in the spillage of glutamate into the extrasynaptic space. Our data show that PNNs and astrocytes cooperate to contain synaptically released signals in physiological conditions. Their combined action is altered in mouse models of Alzheimer’s disease and epilepsy where PNNs are disrupted.

DOI: 10.1038/s41593-024-01714-3

Source: https://www.nature.com/articles/s41593-024-01714-3