Du Y J, Bai Y F, Zhang Y, Liu M, Zhang C Y, Chen Y M, Chen H Y, Li H, Wang G Y
Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2025 Mar 11;105(10):767-772. doi: 10.3760/cma.j.cn112137-20241023-02388.
To investigate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on fear memory and its regulatory role in splenic inflammatory responses in fear-conditioned mice. Twenty-four 12-week-old healthy, male C57BL/6J mice were randomized into two groups using a random number table: taVNS (=12) and control (=12). Both groups underwent conditioned fear modeling using a fear conditioning chamber. The taVNS group received daily taVNS stimulation (dense-disperse wave, 2 Hz/15 Hz, intensity 2 mA, 30 min) for 6 consecutive days, while the control group received sham taVNS (intensity 0 mA, with other parameters identical to the taVNS group). Following two stimulations, the freezing time percentage of contextual fear memory was assessed, along with total distance and time spent in the center zone of the open-field test. After the 4th and 6th stimulations, the freezing time percentage of auditory-cued fear memory was evaluated. Following all behavioral tests, mice were euthanized to measure the spleen index, and levels of interleukin (IL)-1β and IL-10 were measured in both the serum and spleen tissues. After two stimulations, the freezing time percentage of contextual fear memory in the taVNS group was lower than that of the control group (10.7%±8.0% vs 25.8%±14.3%, =0.004), while the total distance [(363.1±125.8) cm vs (234.1±99.2) cm, =0.011] and total time [(39.0±14.7) s vs (23.4±11.6) s, =0.008] in the center zone of the open-field test were higher in the taVNS group. The freezing time percentage of auditory-cued fear memory was lower in the taVNS group compared to the control group after the 4th (36.4%±18.5% vs 58.4%± 21.5%, =0.013) and 6th (30.3%±20.7% vs 63.2%±26.6%, =0.003) stimulations. Serum and splenic IL-1β levels were lower in the taVNS group compared to the control group (all <0.05), while serum and splenic IL-10 levels were higher in the taVNS group (all <0.05). This study indicates that taVNS reduces fear memory in fear-conditioned mice, accompanied by improvements in systemic and splenic inflammatory respcnses, suggesting that splenic inflammatory response may be associated with the effect of taVNS in reducing fear memory.
为研究经皮耳迷走神经刺激（taVNS）对恐惧记忆的影响及其在恐惧条件化小鼠脾脏炎症反应中的调节作用。将24只12周龄健康雄性C57BL/6J小鼠使用随机数字表随机分为两组：taVNS组（n = 12）和对照组（n = 12）。两组均使用恐惧条件化箱进行条件性恐惧建模。taVNS组连续6天每天接受taVNS刺激（疏密波，2 Hz/15 Hz，强度2 mA，30分钟），而对照组接受假taVNS刺激（强度0 mA，其他参数与taVNS组相同）。两次刺激后，评估情境恐惧记忆的冻结时间百分比，以及旷场试验中在中央区域的总距离和停留时间。第4次和第6次刺激后，评估听觉提示恐惧记忆的冻结时间百分比。所有行为测试后，对小鼠实施安乐死以测量脾脏指数，并检测血清和脾脏组织中白细胞介素（IL）-1β和IL-10的水平。两次刺激后，taVNS组情境恐惧记忆的冻结时间百分比低于对照组（10.7%±8.0% 对25.8%±14.3%，P = 0.004），而taVNS组在旷场试验中央区域的总距离[（363.1±125.8）cm对（234.1±99.2）cm，P = 0.011]和总时间[（39.0±14.7）s对（23.4±11.6）s，P = 0.008]更高。第4次（36.4%±18.5%对58.4%±21.5%，P = 0.013）和第6次（30.3%±20.7%对63.2%±26.6%，P = 0.003）刺激后，taVNS组听觉提示恐惧记忆的冻结时间百分比低于对照组。与对照组相比，taVNS组血清和脾脏IL-1β水平较低（均P < 0.05），而taVNS组血清和脾脏IL-10水平较高（均P < 0.05）。本研究表明，taVNS可降低恐惧条件化小鼠的恐惧记忆，并伴有全身和脾脏炎症反应的改善，提示脾脏炎症反应可能与taVNS降低恐惧记忆的作用有关。
