GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model.
GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model.
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在帕金森病模型中，GABA摄取转运蛋白支持背侧纹状体中多巴胺的释放和适应不良的下调。
DOI：
10.1038/s41467-020-18247-5
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发表时间：
2020-10-02
影响因子：
16.6
通讯作者：
Cragg SJ
中科院分区：
文献类型：
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作者：
Roberts BM;Doig NM;Brimblecombe KR;Lopes EF;Siddorn RE;Threlfell S;Connor-Robson N;Bengoa-Vergniory N;Pasternack N;Wade-Martins R;Magill PJ;Cragg SJ
纹状体多巴胺(DA)对行动和学习至关重要。最近的研究表明，纹状体GABA对DA的释放有紧张性抑制作用。位于星形胶质细胞和神经元上的质膜GABA摄取转运体(GATs)可以决定周围纹状体投射神经元上的GABA张力。然而，纹状体Gats和星形胶质细胞是否决定DA的输出尚不清楚。我们发现，小鼠背外侧纹状体的DA释放受GAT-1和GAT-3的控制，而伏隔核核心的DA释放不受GAT-1和GAT-3的控制。这些GATs部分定位于星形胶质细胞，与伏隔核相比，丰富于背外侧纹状体。在早期帕金森病小鼠模型中，GATS表达下调，紧张性GABA能抑制DA释放增强，黑质纹状体GABA协同释放减弱。这些数据明确了Gats和星形胶质细胞在支持纹状体DA释放方面先前未被认识到的重要作用，并揭示了早期帕金森病患者的适应不良可塑性，损害了纹状体脆弱区域的DA输出。纹状体中表达的GABA转运体可能会影响行为。在这里，作者研究了星形胶质细胞上的GABA转运体在纹状体多巴胺释放调节中的作用，并在帕金森病小鼠模型中显示GAT-1和GAT-3的表达减少。
Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release is under tonic inhibition by striatal GABA. Ambient striatal GABA tone on striatal projection neurons can be determined by plasma membrane GABA uptake transporters (GATs) located on astrocytes and neurons. However, whether striatal GATs and astrocytes determine DA output are unknown. We reveal that DA release in mouse dorsolateral striatum, but not nucleus accumbens core, is governed by GAT-1 and GAT-3. These GATs are partly localized to astrocytes, and are enriched in dorsolateral striatum compared to accumbens core. In a mouse model of early parkinsonism, GATs are downregulated, tonic GABAergic inhibition of DA release augmented, and nigrostriatal GABA co-release attenuated. These data define previously unappreciated and important roles for GATs and astrocytes in supporting DA release in striatum, and reveal a maladaptive plasticity in early parkinsonism that impairs DA output in vulnerable striatal regions. GABA transporters expressed in the striatum may affect behaviour. Here the authors investigate the contribution of GABA transporters on astrocytes to the regulation of dopamine release in the striatum, and show decreased expression of GAT-1 and GAT-3 in a mouse model of Parkinsonism.
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影响因子：
5.3
作者：
Cepeda, Carlos;Galvan, Laurie;Levine, Michael S.
通讯作者：
Levine, Michael S.
DOI：
10.1016/s1385-299x(99)00039-2
发表时间：
1999-12-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
--
作者：
Ficková, M;Dahmen, N;Hiemke, C
通讯作者：
Hiemke, C
影响因子：
3.4
作者：
Bonansco, Christian;Couve, Alejandro;Fuenzalida, Marco
通讯作者：
Fuenzalida, Marco
影响因子：
7.3
作者：
Exley, R.;Cragg, S. J.
通讯作者：
Cragg, S. J.
影响因子：
64.8
作者：
通讯作者：
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