腹内侧前额叶皮质锥体神经元参与选择性坐骨神经损伤小鼠疼痛和焦虑样行为调控的研究

doi:10.13418/j.issn.1001-165x.2023.5.10

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中国临床解剖学杂志 ›› 2023, Vol. 41 ›› Issue (5) : 557-564. DOI: 10.13418/j.issn.1001-165x.2023.5.10

实验研究

腹内侧前额叶皮质锥体神经元参与选择性坐骨神经损伤小鼠疼痛和焦虑样行为调控的研究

林培敏¹，刘燕¹，刘婷²，尹颢霖²，张英¹*

作者信息 +

The involvements of pyramidal neurons in ventromedial prefrontal cortex in the regulation of pain and anxiety-like behavior of spared nerve injury mice

Lin Peimin¹, Liu Yan¹, Liu Ting², Yin Haoling², Zhang Ying¹*

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摘要

目的探究腹内侧前额叶皮质（ventromedial prefrontal cortex，vmPFC）锥体神经元对选择性坐骨神经损伤（spared nerve injury，SNI）小鼠疼痛和焦虑样行为的调控作用。方法构建SNI神经病理性疼痛（neuropathic pain，NP）动物模型，假手术组（sham）仅暴露神经。向SNI小鼠损伤对侧腹内侧前额叶皮质（ventromedial prefrontal cortex，vmPFC）注射红藻氨酸/生理盐水，或化学遗传学抑制病毒/空载对照病毒。采用von frey纤维丝检测SNI术后损伤侧机械缩足反射阈值（paw withdrawl threshold，PWT）；高架十字迷宫评估SNI术后焦虑情况；免疫荧光染色观察SNI损伤对侧vmPFC中c-fos表达及注射红藻氨酸后神经元毁损、星形胶质细胞活化情况，RNA-scope原位杂交染色与免疫荧光染色双标明确Vgat基因和Vglut1基因分别与c-fos的共表达情况。结果术后7 d及14 d，相比于sham小鼠，SNI小鼠损伤侧足底PWT、进入开臂次数和停留时间明显减少（P<0.05）；SNI小鼠损伤对侧vmPFC中c-fos阳性神经元数量明显增加，c-fos主要表达在Vglut1基因阳性的神经元（P<0.05）。相比于损伤对侧vmPFC注射生理盐水的SNI小鼠，注射红藻氨酸的SNI小鼠损伤对侧vmPFC中出现明显的神经元毁损及星形胶质细胞活化现象，损伤侧足底PWT、进入开臂次数和时间明显增加（P<0.05）。此外，化学遗传学策略抑制SNI小鼠损伤对侧vmPFC的锥体神经元后，SNI小鼠损伤对侧vmPFC中c-fos阳性神经元数量明显减少，同时损伤侧足底PWT、进入开臂次数和时间明显增加（P<0.05）。结论 SNI小鼠损伤对侧vmPFC中的锥体神经元影响疼痛及焦虑样行为的发生发展。

Abstract

Objective To explore the role of pyramidal neurons of ventromedial prefrontal cortex (vmPFC) in pain and anxiety-like behavior of spared nerve injury (SNI) mice. Methods Spared nerve injury (SNI) was used to mimic neuropathic pain (NP) animal model, while a same incision without nerve injury was performed to establish the sham control group. Kainic aicd, normal saline, AAV2/9 virus were intracranially injected into contralateral vmPFC of SNI mice. Von frey filaments were used to detect the paw withdraw threshold (PWT) of the ipsilateral planta of SNI mice. The elevated plus maze (EPM) was used to assess anxiety behaviors of SNI mice. Immunofluorescence staining was used to observe the expression of c-fos, the neuronal loss and the astrocytic activation in the contralateral vmPFC. RNA-scope and immunofluorescence staining were used to identify the neuronal type of c-fos positive neuron of vmPFC. Results Compared with sham mice, ipsilateral PWT, entries in open arms and cumulative duration in open arms of SNI mice were significantly decreased at 7d and 14d after SNI (P<0.05). Compared with sham mice, c-fos positive neurons were significantly increased in the contralateral of vmPFC of SNI mice (P<0.05). In addition, the c-fos positive neurons were almost Vglut1 positive neurons. Compared with the SNI mice which intracranially injected into contraleral vmPFC with normal saline, ipsilateral PWT, entries in open arms and cumulative duration in open arms of the SNI mice which intracranially injected into contraleral vmPFC with kainic acid were increased (P<0.05). Meanwhile, the SNI mice which intracranially injected into contraleral vmPFC with kainic acid exhibited obvious neuronal loss and astrocytic activation in the contralateral vmPFC. In addition, using chemogenetics strategy to inhibit the pyramidal neurons in contralateral vmPFC of SNI mice, the c-fos positive neurons were significantly deceased, the ipsilateral PWT, entries in open arms and cumulative duration in open arms were significantly increased (P<0.05). Conclusions Pyramidal neurons in the contralateral vmPFC may be involved in the development of pain and anxiety-like behaviors of SNI mice.

导出引用

林培敏, 刘燕, 刘婷, 尹颢霖, 张英. 腹内侧前额叶皮质锥体神经元参与选择性坐骨神经损伤小鼠疼痛和焦虑样行为调控的研究[J]. 中国临床解剖学杂志. 2023, 41(5): 557-564 https://doi.org/10.13418/j.issn.1001-165x.2023.5.10

Lin Peimin, Liu Yan, Liu Ting, Yin Haoling, Zhang Ying. The involvements of pyramidal neurons in ventromedial prefrontal cortex in the regulation of pain and anxiety-like behavior of spared nerve injury mice[J]. Chinese Journal of Clinical Anatomy. 2023, 41(5): 557-564 https://doi.org/10.13418/j.issn.1001-165x.2023.5.10

中图分类号： R338

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