UK Dementia Research Institute at the University of Edinburgh, Chancellor's Building, Edinburgh Medical School, Edinburgh EH16 4SB, UK.
Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
Int J Mol Sci. 2020 Dec 17;21(24):9607. doi: 10.3390/ijms21249607.
The astrocytic glutamate transporters excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2) play a key role in nervous system function to maintain extracellular glutamate levels at low levels. In physiology, this is essential for the rapid uptake of synaptically released glutamate, maintaining the temporal fidelity of synaptic transmission. However, EAAT1/2 hypo-expression or hypo-function are implicated in several disorders, including epilepsy and neurodegenerative diseases, as well as being observed naturally with aging. This not only disrupts synaptic information transmission, but in extremis leads to extracellular glutamate accumulation and excitotoxicity. A key facet of EAAT1/2 expression in astrocytes is a requirement for signals from other brain cell types in order to maintain their expression. Recent evidence has shown a prominent role for contact-dependent neuron-to-astrocyte and/or endothelial cell-to-astrocyte Notch signalling for inducing and maintaining the expression of these astrocytic glutamate transporters. The relevance of this non-cell-autonomous dependence to age- and neurodegenerative disease-associated decline in astrocytic EAAT expression is discussed, plus the implications for disease progression and putative therapeutic strategies.
星形细胞谷氨酸转运体兴奋性氨基酸转运体 1 和 2（EAAT1 和 EAAT2）在神经系统功能中发挥着关键作用，可将细胞外谷氨酸水平维持在低水平。在生理学上，这对于快速摄取突触释放的谷氨酸，维持突触传递的时间准确性至关重要。然而，EAAT1/2 的低表达或功能障碍与多种疾病有关，包括癫痫和神经退行性疾病，并且随着年龄的增长自然观察到。这不仅破坏了突触信息传递，而且在极端情况下导致细胞外谷氨酸积累和兴奋性毒性。星形细胞中 EAAT1/2 表达的一个关键方面是需要来自其他脑细胞类型的信号来维持其表达。最近的证据表明，接触依赖性神经元-星形细胞和/或内皮细胞-星形细胞 Notch 信号在诱导和维持这些星形细胞谷氨酸转运体的表达中起着重要作用。讨论了这种非细胞自主依赖性与星形细胞 EAAT 表达与年龄和神经退行性疾病相关下降的相关性，以及对疾病进展和潜在治疗策略的影响。
