BzATP Activates Satellite Glial Cells and Increases the Excitability of Dorsal Root Ganglia Neurons In Vivo.
BzATP Activates Satellite Glial Cells and Increases the Excitability of Dorsal Root Ganglia Neurons In Vivo.
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BzATP激活卫星神经胶质细胞，提高背根神经节神经元的兴奋性。
DOI：
10.3390/cells11152280
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发表时间：
2022-07-23
期刊：
影响因子：
6
通讯作者：
Guan, Yun
中科院分区：
文献类型：
--
作者：
Chen, Zhiyong;Zhang, Chi;Song, Xiaodan;Cui, Xiang;Liu, Jing;Ford, Neil C.;He, Shaoqiu;Zhu, Guangwu;Dong, Xinzhong;Hanani, Menachem;Guan, Yun
嘌呤能系统在痛觉传递中起重要作用。最近的研究表明，P2-嘌呤能受体（P2 Rs）的激活可能参与背根神经节（DRG）的神经元-卫星胶质细胞（SGC）的相互作用，但细节尚不清楚。在DRG中，P2 X7 R选择性地表达于紧密围绕神经元的SGCs中，并且对3 '-O-（4-Benzoyl）benzoyl-ATP（BzATP）高度敏感。在完整的小鼠使用钙成像调查了大量的DRG神经元和SGCs，我们研究了如何在神经节内嘌呤信号BzATP启动影响体内神经元的活动。我们开发了GFAP-GCaMP 6s和Pirt-GCaMP 6s小鼠，分别在SGCs和DRG神经元中表达遗传编码的钙指示剂GGCaM 6s。在GFAP-GCaMP 6s小鼠中，BzATP对神经节的应用诱导了SGCs的浓度依赖性活化。在Pirt-GCaMP 6s小鼠中，BzATP最初激活的大尺寸神经元多于小尺寸神经元。P2 X7 R选择性拮抗剂A438079可阻断BzATP对胶质细胞和神经元的反应。此外，pannexin 1通道阻断剂（丙磺舒）和P2 X3 R（A317491）也降低了BzATP的作用，表明P2 X7 R刺激可能诱导pannexin 1通道开放，导致旁分泌ATP释放，这可能通过作用于P2 X3 R进一步兴奋神经元。重要的是，BzATP增加了小尺寸DRG神经元和宽动态范围脊髓神经元对随后的外周刺激的反应。我们的研究结果表明，P2 X7 R激活启动的神经节内嘌呤能信号可以触发体内SGC-神经元相互作用，并增加DRG神经元的兴奋性。
The purinergic system plays an important role in pain transmission. Recent studies have suggested that activation of P2-purinergic receptors (P2Rs) may be involved in neuron-satellite glial cell (SGC) interactions in the dorsal root ganglia (DRG), but the details remain unclear. In DRG, P2X7R is selectively expressed in SGCs, which closely surround neurons, and is highly sensitive to 3’-O-(4-Benzoyl) benzoyl-ATP (BzATP). Using calcium imaging in intact mice to survey a large number of DRG neurons and SGCs, we examined how intra-ganglionic purinergic signaling initiated by BzATP affects neuronal activities in vivo. We developed GFAP-GCaMP6s and Pirt-GCaMP6s mice to express the genetically encoded calcium indicator GGCaM6s in SGCs and DRG neurons, respectively. The application of BzATP to the ganglion induced concentration-dependent activation of SGCs in GFAP-GCaMP6s mice. In Pirt-GCaMP6s mice, BzATP initially activated more large-size neurons than small-size ones. Both glial and neuronal responses to BzATP were blocked by A438079, a P2X7R-selective antagonist. Moreover, blockers to pannexin1 channels (probenecid) and P2X3R (A317491) also reduced the actions of BzATP, suggesting that P2X7R stimulation may induce the opening of pannexin1 channels, leading to paracrine ATP release, which could further excite neurons by acting on P2X3Rs. Importantly, BzATP increased the responses of small-size DRG neurons and wide-dynamic range spinal neurons to subsequent peripheral stimuli. Our findings suggest that intra-ganglionic purinergic signaling initiated by P2X7R activation could trigger SGC-neuron interaction in vivo and increase DRG neuron excitability.
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影响因子：
5.6
作者：
Burnstock G
通讯作者：
Burnstock G
感觉神经节内的局部 GABA 信号传导控制外周伤害性传递。
DOI：
10.1172/jci86812
发表时间：
2017-05-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Du X;Hao H;Yang Y;Huang S;Wang C;Gigout S;Ramli R;Li X;Jaworska E;Edwards I;Deuchars J;Yanagawa Y;Qi J;Guan B;Jaffe DB;Zhang H;Gamper N
通讯作者：
Gamper N
影响因子：
3.7
作者：
Bhaskaracharya A;Dao-Ung P;Jalilian I;Spildrejorde M;Skarratt KK;Fuller SJ;Sluyter R;Stokes L
通讯作者：
Stokes L
影响因子：
2.5
作者：
Guo, Tiantian;Bian, Zichao;Feng, Bin
通讯作者：
Feng, Bin
影响因子：
16.2
作者：
Grienberger, Christine;Konnerth, Arthur
通讯作者：
Konnerth, Arthur