Yang Sanjuan, Li Junyao, Han Lan, Zhu Guoqi
Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine Hefei 230038, China.
School of Pharmacy, Anhui University of Chinese Medicine Hefei 230038, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10812-10820. eCollection 2017.
Adverse early-life experience such as maternal separation (MS) affects the behavior of adult, and may also aggravate the outcome of neurological insults. In this study, we aimed to investigate the effects of early MS on hippocampus-related behaviors, and to assess the mechanisms. Newborn rats were randomly divided into normal control and MS groups. Our data showed that MS (P3-P21) impaired learning ability as well as memory retrieval, and caused depression-like activity, but decreased anxiety-like activity. Glutamate receptor 1 (GluR1) expression in the dentate gyrus (DG) region was significantly reduced in the adults (P60). Mechanically, MS promoted apoptosis, and reduced protein kinase B (AKT) phosphorylation in the DG region in the early phase (P21). By contrast, MS did not affect ERK phosphorylation. Our data implicate that the inactivation of AKT pathway and apoptosis of DG cells might contribute to MS-induced behavioral changes. This study would provide useful evidence implicating the pathological changes for MS.
早期生活中的不良经历，如母婴分离（MS），会影响成年后的行为，还可能加重神经损伤的后果。在本研究中，我们旨在探讨早期母婴分离对海马体相关行为的影响，并评估其机制。新生大鼠被随机分为正常对照组和母婴分离组。我们的数据表明，母婴分离（P3 - P21）会损害学习能力和记忆提取，并导致类似抑郁的行为，但会降低类似焦虑的行为。成年大鼠（P60）齿状回（DG）区域的谷氨酸受体1（GluR1）表达显著降低。从机制上讲，母婴分离在早期（P21）促进了细胞凋亡，并降低了齿状回区域蛋白激酶B（AKT）的磷酸化。相比之下，母婴分离不影响细胞外信号调节激酶（ERK）的磷酸化。我们的数据表明，AKT通路的失活和齿状回细胞的凋亡可能导致母婴分离诱导的行为变化。本研究将为母婴分离的病理变化提供有用的证据。
