Dep. Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77 Stockholm, Sweden.
Dep. Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Cells. 2020 Jul 16;9(7):1705. doi: 10.3390/cells9071705.
A decrease in synaptic plasticity and/or a change in excitation/inhibition balance have been suggested as mechanisms underlying major depression disorder. However, given the crucial role of astrocytes in balancing synaptic function, particular attention should be given to the contribution of astrocytes in these mechanisms, especially since previous findings show that astrocytes are affected and exhibit reactive-like features in depression. Moreover, it has been shown that reactive astrocytes increase the synthesis and release of GABA, contributing significantly to tonic GABA inhibition. In this study we found decreased plasticity and increased tonic GABA inhibition in the prelimbic area in acute slices from the medial prefrontal cortex in the Flinders Sensitive Line (FSL) rat model of depression. The tonic inhibition can be reduced by either blocking astrocytic intracellular Ca signaling or by reducing astrocytic GABA through inhibition of the synthesizing enzyme MAO-B with Selegiline. Blocking GABA synthesis also restores the impaired synaptic plasticity in the FSL prefrontal cortex, providing a new antidepressant mechanism of Selegiline.
突触可塑性降低和/或兴奋/抑制平衡改变被认为是导致重度抑郁症的机制。然而，鉴于星形胶质细胞在平衡突触功能方面的关键作用，应该特别关注星形胶质细胞在这些机制中的贡献，特别是因为之前的研究发现星形胶质细胞受到影响，并表现出抑郁样特征。此外，已经表明反应性星形胶质细胞增加 GABA 的合成和释放，对紧张性 GABA 抑制有重要贡献。在这项研究中，我们发现抑郁的弗林德斯敏感线（FSL）大鼠模型的内侧前额叶皮质的急性切片中的前扣带皮层的可塑性降低和紧张性 GABA 抑制增加。通过阻断星形胶质细胞细胞内 Ca 信号或通过抑制合成酶 MAO-B 用司来吉兰减少星形胶质细胞 GABA，可降低紧张性抑制。阻断 GABA 合成也恢复了 FSL 前额叶皮质受损的突触可塑性，为司来吉兰提供了一种新的抗抑郁机制。
