陆军军医大学学报2026，Vol.48Issue(4)：394-406,13.DOI:10.16016/j.2097-0927.202511032
选择性过表达海马CB1R缓解慢性应激诱导的神经发生减弱及行为学损伤
Selective overexpression of hippocampal CB1R alleviates chronic stress-induced neurogenesis impairment and behavior disorder in rats
摘要
Abstract
Objective To investigate the effects of selective overexpression of hippocampal cannabinoid receptor 1(CB1R)on newly generated cells and newly matured neurons in the hippocampus of stress-induced rats.Methods Thirty-two 6-8 week-old male SD rats(body weight 180 to 220 g)were randomly assigned to a Control group(n=10)and a Stress group(n=22).After the Stress group underwent 3 weeks of chronic restraint stress(CRS),11 rats were randomly selected to form the Stress+CB1R-OE group,receiving hippocampal injections of an adeno-associated virus(AAV)for CB1R overexpression via stereotaxic surgery.The Control group and the remaining Stress group received a null AAV,designated as Control+AAV-NC and Stress+AAV-NC groups,respectively;viral transfection lasted 3 weeks.Body weight was measured every Sunday morning for weeks 1 to 7.Behavioral levels were assessed using the novel environment feeding suppression test.Immunofluorescence staining was used to detect the expression of 5-bromo-2'-deoxyuridine(BrdU),Neuronal Nuclei(NeuN),and CB1R in the hippocampal dentate gyrus(DG)(n=5 per group,3 slices per rat).A NOVEL confocal microscope was used for scanning.Imaris software calculated the density of BrdU+and BrdU+/NeuN+ cells per unit volume in the DG,while Image J software measured the mean fluorescence intensity of CB1R and NeuN in the DG.Western blot assay was used to detect hippocampal CB1R protein expression levels.Results After 3 weeks of CRS,the body weight of the Stress+AAV-NC group was significantly lower than that of the Control+AAV-NC group(P=0.001).Selective hippocampal CB1R overexpression for 3 weeks partially ameliorated body weight gain in the Stress+CB1R-OE group,but their weight remained significantly lower than the Control+AAV-NC group(P=0.004).The novel environment feeding suppression test showed that compared to the Control+AAV-NC group,the Stress+AAV-NC group had a significantly prolonged feeding latency(P＜0.001),with no significant difference in feeding amount within 5 min.After selective CB1R overexpression,the Stress+CB1R-OE group showed a significantly shortened feeding latency(P=0.039),with no significant differences in feeding amount among the three groups.Immunofluorescence results indicated that compared to the Control+AAV-NC group,the Stress+AAV-NC group had a significantly reduced mean fluorescence intensity of CB1R+ cells in the DG(P=0.008).After selective CB1R overexpression,the Stress+CB1R-OE group showed a significantly increased mean CB1R fluorescence intensity in the DG compared to the Stress+AAV-NC group(P＜0.001).Western blotting results showed that hippocampal CB1R protein expression was significantly lower in the Stress+AAV-NC group than in the Control+AAV-NC group(P=0.001).Compared to the Stress+AAV-NC group,the Stress+CB1R-OE group had a significantly increased hippocampal CB1R expression level(P＜0.001).Compared to the Control+AAV-NC group,the Stress+AAV-NC group had reduced densities of BrdU+ newborn cells(P=0.003)and BrdU+/NeuN+newly matured neurons(P=0.001)in the DG.After selective CB1R overexpression,the Stress+CB1R-OE group showed significantly increased densities of BrdU+ cells(P=0.035)and BrdU+/NeuN+ neurons(P=0.028)in the DG.No significant difference was observed in the mean NeuN fluorescence intensity in the DG among the three groups.Conclusion Selective overexpression of hippocampal CB1R can alleviate stress-mediated reduction in hippocampal neurogenesis and subsequently improve behavioral deficits in stress-induced rats.关键词
应激/海马体/成体海马神经发生/大麻素受体1Key words
stress/hippocampus/adult hippocampal neurogenesis/cannabinoid receptor 1分类
医药卫生引用本文复制引用
游娅君,陈艳,黄杜娟,蒋林,邓宇辉,周宇宁,唐勇,肖倩..选择性过表达海马CB1R缓解慢性应激诱导的神经发生减弱及行为学损伤[J].陆军军医大学学报,2026,48(4):394-406,13.基金项目
国家自然科学基金面上项目(82171522) （82171522）
国家自然科学基金青年科学基金项目(82001435) （82001435）
重庆市自然科学基金博士后科学基金项目(cstc2020jcyj-bshX0098) Supported by the General Program of National Natural Science Foundation of China(82171522),the National Natural Science Foundation for Young Scholars of China(82001435)and the Postdoctoral Program of Chongqing Natural Science Foundation(cstc2020jcyj-bshX0098). （cstc2020jcyj-bshX0098）
