AAV-srGAP3 was used for overexpression of SrGAP3. (From
BrainVTA)
The viruses used from BrainVTA in this article are in the table below
|
Custom-Made AAVs |
rAAV9-CMV-DIO-srGAP3-3 × FLAG-WPRE-pA
rAAV9-TRE3G-srGAP3-3×FLAG-WPRE-pA |
|
CRE Recombinase |
PT-0136 rAAV9-hSyn-CRE-WPRE-pA |
|
Control |
PT-0310 rAAV9-CMV-DIO-WPRE-pA
rAAV9-hSyn-rTTA-WPRE-pA
PT-0241 rAAV9-hSyn-WPRE-pA |
Zihang Chen, Subo Zhang, Bilin Nie, Jingxiu Huang, Zhixiao Han, Xiaodi Chen, Xiaohui Bai, Handong Ouyang
Pub Date: 2020-04-01,
DOI: 10.1113/jp279525,
Email: [email protected]
Neuropathic pain includes an initiation phase and maintenance phase, each with different pathophysiological processes. Understanding the synaptic plasticity and molecular events in these two phases is relevant to exploring precise treatment strategies for neuropathic pain. In the present study, we show that dendritic spine density increases in the spinal dorsal horn in the initiation phase of neuropathic pain induced by paclitaxel and that the spine maturity ratio increases in the maintenance phase. Increased srGAP3 (slit-robo GTPase activating protein 3) facilitates dendritic spine sprouting in the initiation phase. In the maintenance phase, srGAP3 decreases to upregulate Rac1 activity, which facilitates actin polymerization and dendritic spine maturation and thus the persistence of neuropathic pain. Knockdown of srGAP3 in the initiation phase or inhibition of Rac1 in the maintenance phase attenuates neuropathic pain. Combined intervention of srGAP3 in the initiation phase, and Rac1 in the maintenance phase shows better analgesic efficacy against neuropathic pain. The present study demonstrates the role of srGAP3-Rac1 in dendritic spine plasticity in the two phases of neuropathic pain and, accordingly, provides treatment strategies for different phases of neuropathic pain.
Figure 1. Paclitaxel induced marked mechanical allodynia, spine plasticity and changes of srGAP3 Expression.
This study is aimed to explore the transformation and mechanisms of dendritic spines in different
phases of neuropathic pain. In the present study, the authors used a paclitaxel-induced neuropathic pain model to reveal the number and morphological changes of dendritic spines in the initiation and maintenance phases of neuropathic pain, as well as in analyses of the molecular mechanisms of the srGAP3/Rac1 pathway. The results of the study provide a theoretical basis and molecular target for the precise treatment of the two phases of neuropathic pain.
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