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| 艾司氯胺酮对抑郁小鼠锥体神经元网络连接水平的影响 |
| Effects of esketamine on the network connectivity of pyramidal neurons in depressed mice |
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| DOI：10.12089/jca.2025.10.015 |
| 中文关键词: 抑郁 艾司氯胺酮 内侧前额叶皮层 锥体神经元 |
| 英文关键词: Depression Esketamine Medial prefrontal cortex Pyramidal neurons |
| 基金项目:国家自然科学基金面上项目（82372182、82172131） |
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| 中文摘要: |
目的：探讨艾司氯胺酮对小鼠抑郁行为及内侧前额叶皮层（mPFC）锥体神经元活性和网络连接水平的影响。
方法：选择雄性C57BL/6J小鼠7只，7周龄，体重18～23 g。对小鼠进行mPFC脑区立体定位手术和微型双光子显微镜固定手术，术后5周进行持续21 d的慢性束缚应激（CRS）建立抑郁小鼠模型，模型建立后对小鼠进行腹腔注射艾司氯胺酮5 mg/kg。于术后5周（建模前）、建模后、注射艾司氯胺酮1 h后（用药后）记录微型双光子钙成像信号，通过mPFC脑区同步锥体神经元数目和同步性衡量小鼠mPFC脑区锥体神经元网络连接水平。
结果：与建模前比较，建模后小鼠mPFC脑区锥体神经元钙瞬变活性及锥体神经元同步性明显降低（P＜0.05），同步锥体神经元数目明显减少、同步性明显降低（P＜0.05）。与建模后比较，用药后小鼠mPFC锥体神经元同步性明显升高（P＜0.05），同步锥体神经元数目明显增多、同步性明显升高（P<0.05）。
结论：艾司氯胺酮可能通过提高小鼠mPFC脑区锥体神经元网络连接水平，发挥快速抗抑郁作用。 |
| 英文摘要: |
Objective: To investigate the effects of esketamine on depressive behaviors and on the activity and network connectivity of pyramidal neurons in the medial prefrontal cortex (mPFC) of mice.
Methods: Seven male C57BL/6J mice, aged 7 weeks, weighing 18-23 g, were selected. The mice underwent stereotactic surgery targeting the mPFC and implantation of a miniature two-photon microscope. After a 5-week recovery period, the mice were subjected to 21 days of chronic restraint stress (CRS) to establish a depression model. Upon completion of the model, the mice received an intraperitoneal injection of esketamine 5 mg/kg. Miniature two-photon calcium imaging signals were recorded at three time points: 5 weeks post-surgery (pre-modeling), post-modeling, and 1-hour post-esketamine administration (post-administration). The connection level of pyramidal neuron networks in the mPFC was measured by the number of synchronous pyramidal neurons and their synchrony within the mPFC.
Results: Compared with the pre-modeling, both the calcium transient activity and synchrony of pyramidal neurons in the mPFC were significantly decreased post-modeling (P < 0.05), the number of synchronous pyramidal neurons was significantly decreased, and synchrony was significantly reduced (P < 0.05). Compared with the post-modeling, the synchrony of pyramidal neurons in the mPFC was significantly increased post-administration (P < 0.05), the number of synchronous pyramidal neurons was significantly increased, and synchrony was significantly enhanced (P < 0.05).
Conclusion: Esketamine may exert rapid antidepressant effects by enhancing the network connectivity of pyramidal neurons in the mPFC of mice. |
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