Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1
Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1
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母体分离所致成年大鼠雌性依赖性恐惧记忆受损及海马CA1区可能相关基因的筛选
DOI：
10.1016/j.bbr.2014.03.022
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发表时间：
2014-07
影响因子：
2.7
通讯作者：
Hu Zhao
中科院分区：
文献类型：
--
作者：
Wen-Qiang Tu;Yan-Wei Shi;Li Xue;Hu Zhao
早期生活压力是导致创伤后应激障碍（PTSD）等应激相关疾病的主要易感因素之一。最近对大鼠的研究表明，早期生活压力可能会使生物体在以后的生活中以最佳方式应对压力环境，而不是总体上不利。本研究通过连续六小时的母亲分离（MS），从PND 1到PND 21，进行严重不良的早期生活压力，并在PND 90使用情境恐惧条件反射模型来模拟成年后的第二次压力和创伤后应激障碍的再体验症状。据观察，在这项调查中，经历MS的幼崽在成年期表现出对情境恐惧条件反射的敏感性降低，性别在其中起着重要作用。例如，患有MS的雌性大鼠比雄性和对照组的冻结率低得多。Morris水迷宫实验表明MS对大鼠的空间学习记忆能力无明显影响。采用抑制性消减杂交（suppression subtractive hybridization，SSH）技术，通过检测情境恐惧条件化后MS雌性大鼠和对照组大鼠海马CA 1区mRNA表达的变化，筛选恐惧记忆相关基因。最终发现9个基因表达上调，1个基因表达下调，包括β2-MG、MAF、Nd 1-L、TorsinA和MACF 1基因。推测TorsinA、MACF 1和Nd 1-L基因可能与MS诱导的PTSD敏感性降低有关。
Early life stress is one of the major susceptible factors for stress-related pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats suggest that rather than being overall unfavorable, early life stress may prepare the organism to perform optimally to stressful environments later in life. In this study, severely adverse early life stress was conducted by six consecutive hours of maternal separation (MS), from PND1 to PND21, and contextual fear conditioning model was used on PND90 to mimic the second stress in adulthood and the re-experiencing symptom of PTSD. It was observed that in this investigation pups experienced MS showed decreased sensibility to contextual fear conditioning in adulthood, and there sex plays an important role. For example, female rats suffered MS had much lower freezing than males and controls. Meanwhile, Morris water maze test indicated that MS did not impair rat's performance of spatial learning and memory. Furthermore, suppression subtractive hybridization (SSH) was used to screen the related genes of fear memory, by examining the changes of mRNA expression in CA1 area between female MS and control rats after contextual fear conditioning. Finally, nine up-regulated and one down-regulated genes, including β2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased sensitivity of PTSD induced by MS.
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