海马腹侧成体神经干细胞在急性社交压力恐惧记忆消退中的作用

Role of neural stem cells in the ventral hippocampus in the fear memory extinction related to acute social stress

目的探讨海马腹侧区成体神经干细胞在社交压力相关的伤害性记忆消退过程中是否发挥作用。方法将C57B/L成年雄性小鼠分为3组:对照组、急性社交压力组和海马腹侧区X线照射联合急性社交压力组。其中海马腹侧区X线照射联合急性社交压力组小鼠在社交压力刺激前第5、3、1天分别用X线照射海马腹侧区。在急性社交压力刺激后第7天通过行为学测试检测小鼠的社交时间、探索距离;通过免疫荧光组织化学技术检测小鼠海马区双肾上腺皮质激素阳性细胞数量;通过实时聚合酶链反应技术检测小鼠海马区脑源性神经营养因子(BDNF)、胰岛素样生长因子2 (IGF2)和环磷腺苷效应元件结合蛋白(CREB)的表达水平。结果急性社交压力组小鼠在急性社交压力刺激后第7天社交时间和探索距离均减少(P<0.05),海马腹侧区X线照射联合社交压力组社交时间和探索距离减少更明显(P<0.01);急性社交压力组和海马腹侧区X线照射联合急性社交压力组小鼠海马区双肾上腺皮质激素阳性细胞均减少,其中海马腹侧区X线照射联合急性社交压力组减少更明显(P<0.01);急性社交压力组小鼠海马区BDNF表达量明显下调(P<0.01),海马腹侧区X线照射联合急性社交压力组IGF2表达量明显下调(P<0.01)。结论损伤海马腹侧区成体神经干细胞会导致社交压力相关的伤害性记忆消退延迟,表明海马腹侧区神经干细胞参与了伤害性信息处理。

Objective To investigate whether adult neural stem cells in the ventral hippocampus play a role in the process of nociceptive memory fading related to social stress. Methods C57 B/L adult male mice were divided into three groups: the control group, the acute social stress group, and the hippocampal ventral X-ray irradiation combined with acute social stress group. The mice in the hippocampal ventral X-ray irradiation ombined with acute social stress group were irradiated with X-rays to the hippocampal ventral area on the5 th, 3 rd and 1 st day before the social stress stimulation. On the 7 th day after the acute social stress stimulation, the social time and exploration distance of the mice were detected by behavioral tests;the number of DCX-positive cells in the hippocampus of mice was detected by immunofluorescence histochemistry;the hippocampus of mice was detected by real-time PCR technology for the expression levels of BDNF, IGF2 and CREB. Results The social time and exploration distance of mice in the acute social stress group decreased on the 7 th day after the acute social stress stimulation(P < 0.05), and the social time and exploration distance of the hippocampal ventral X-ray irradiation combined with acute social stress group decreased more significantly(P < 0.01);the DCX positive cells in the hippocampus of the mice in the acute social stress group and the hippocampal ventral X-ray irradiation combined with acute social stress group were reduced, and the hippocampal ventral X-ray irradiation combined with acute social stress group decreased more significantly(P < 0.01);the expression of BDNF in the hippocampus of the mouse in the acute social stress group was obvious. It was down-regulated(P < 0.01), and the expression of IGF2 in the hippocampal ventral X-ray irradiation combined with acute social stress group was significantly down-regulated(P < 0.01). Conclusion Injury to adult neural stem cells in the ventral hippocampus can lead to a delay in the disappearance of nociceptive memories related to social stress, indicating that neural stem cells in the ventral hippocampus are involved in nociceptive information processing.