Han Wei, Dong Xiangjun, Song Xiaojie, Cheng Li, Xie Lingling, Chen Hengsheng, Jiang Li
Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, PR China.
Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, PR China; Department of Neurology, Children's Hospital of Chongqing Medical University, 136# Zhongshan 2nd Road, Chongqing, 400014, PR China.
Behav Brain Res. 2018 Nov 1;353:218-226. doi: 10.1016/j.bbr.2018.04.003. Epub 2018 Apr 4.
Due to socio-economic development, an increasing number of women delay childbirth to their late 30 s and older. However, this delay brings a series of health problems to pregnant women and their offspring. The few studies on the effects of advanced maternal age (AMA) on offspring development, especially regarding neurocognitive and emotional development, reported mixed results. We examined the relationship between AMA and the performance of immature offspring of 3- versus 12-month-old Sprague-Dawley rat females on neurocognitive development tests and the possible mechanism of this relationship; the rats were individually housed with a randomly selected 3-month-old male, and the cognitive development of the offspring was evaluated by behavior tests including the Morris water maze, elevated plus maze, forced swimming and 3-chambered social behavior tests. Moreover, hematoxylin-eosin (HE) staining and Nissl staining were conducted to detect differences in the hippocampal morphology of the offspring, and Western blot analysis was conducted to detect the protein expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB) and phosphorylated CREB (pCREB). The behavior tests detected defects in the AMA rats compared with the control group. The HE and Nissl staining results showed no significant difference. However, the expression of BDNF, CREB and pCREB was reduced in the immature offspring of AMA rats compared with that in control rats. Based on our results, CREB-dependent expression of BDNF may be responsible for the damage to cognitive and emotional development in offspring caused by delayed motherhood.
由于社会经济发展，越来越多的女性将生育推迟到30多岁及更晚。然而，这种延迟给孕妇及其后代带来了一系列健康问题。关于高龄产妇（AMA）对后代发育影响的少数研究，特别是在神经认知和情感发育方面，结果不一。我们研究了AMA与3月龄和12月龄斯普拉格-道利大鼠雌性未成熟后代在神经认知发育测试中的表现之间的关系以及这种关系的可能机制；将大鼠单独饲养，并与随机选择的3月龄雄性大鼠配对，通过包括莫里斯水迷宫、高架十字迷宫、强迫游泳和三室社交行为测试在内的行为测试评估后代的认知发育。此外，进行苏木精-伊红（HE）染色和尼氏染色以检测后代海马形态的差异，并进行蛋白质印迹分析以检测脑源性神经营养因子（BDNF）、环磷腺苷反应元件结合蛋白（CREB）和磷酸化CREB（pCREB）的蛋白表达。行为测试发现与对照组相比，AMA大鼠存在缺陷。HE和尼氏染色结果显示无显著差异。然而，与对照大鼠相比，AMA大鼠未成熟后代中BDNF、CREB和pCREB的表达降低。根据我们的结果，BDNF的CREB依赖性表达可能是导致母亲生育延迟对后代认知和情感发育造成损害的原因。
