Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging
Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging
复制标题
DOI：
10.1042/bst20140163
复制
发表时间：
2014-10-01
影响因子：
3.9
通讯作者：
Pankratov, Yuriy
中科院分区：
文献类型：
--
作者：
Lalo, Ulyana;Rasooli-Nejad, Seyed;Pankratov, Yuriy
在衰老过程中保持大脑功能对身心健康非常重要。最近的研究表明，两种主要类型的脑细胞之间的通信至关重要：神经元传输电信号，神经胶质细胞维持神经元的健康和功能。尽管如此，神经胶质细胞信号与年龄相关的变化的研究还远未完成。我们以前已经表明，皮质星形胶质细胞能够释放ATP的量子可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复杂的依赖性机制。ATP从皮质星形胶质细胞的释放可以通过多种途径激活，包括细胞内Ca 2+或G蛋白偶联受体的直接UV-释放。重要的是，在显性负性SNARE（dnSNARE）小鼠的脑切片中没有观察到新皮层星形胶质细胞释放ATP和谷氨酸，在星形胶质细胞中选择性表达dnSNARE结构域。我们还发现，星形胶质细胞驱动的ATP可以通过神经元ATP和γ-氨基丁酸（GABA）受体之间的Ca 2+相互作用引起锥体神经元突触抑制的显着衰减。此外，我们发现星形胶质细胞来源的ATP可以促进新皮层突触可塑性的长时程增强的诱导。我们最近的数据表明，年龄相关的减少星形胶质细胞Ca 2+信号可以导致大量减少的胞吐的胶质递质，特别是ATP。皮层星形胶质细胞ATP释放的年龄相关损伤可导致新皮层中突触传递的星形胶质细胞调节程度降低，因此可导致突触可塑性和认知能力下降的年龄相关损伤。结合，我们的研究结果强烈支持神经胶质细胞胞吐的神经胶质细胞神经元通信和脑功能的生理相关性。
Maintaining brain function during aging is very important for mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals, and glial cells, which maintain the well-being and function of neurons. Still, the study of age-related changes in neuron-glia signalling is far from complete. We have shown previously that cortical astrocytes are capable of releasing ATP by a quantal soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complex-dependent mechanism. Release of ATP from cortical astrocytes can be activated via various pathways, including direct UV-uncaging of intracellular Ca2+ or G-protein-coupled receptors. Importantly, release of both ATP and glutamate from neocortical astrocytes was not observed in brain slices of dominant-negative SNARE (dnSNARE) mice, expressing dnSNARE domain selectively in astrocytes. We also discovered that astrocyte-driven ATP can cause significant attenuation of synaptic inhibition in the pyramidal neurons via Ca2+-interaction between the neuronal ATP and gamma-aminobutyric acid (GABA) receptors. Furthermore, we showed that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Our recent data have shown that an age-related decrease in the astroglial Ca2+ signalling can cause a substantial decrease in the exocytosis of gliotransmitters, in particular ATP. Age-related impairment of ATP release from cortical astrocytes can cause a decrease in the extent of astroglial modulation of synaptic transmission in the neocortex and can therefore contribute to the age-related impairment of synaptic plasticity and cognitive decline. Combined, our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function.