Liu Xueyuan, Zhao Wenlong, Liu Haiyan, Kang Yaoyue, Ye Chen, Gu Weirong, Hu Rong, Li Xiaotian
Obstetrics and Gynecology Hospital of Fudan University, 200011, Shanghai, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
Mol Neurobiol. 2016 Mar;53(2):1009-1019. doi: 10.1007/s12035-014-9060-7. Epub 2015 Jan 10.
Preeclampsia is associated with developmental delay in infants and with an increased risk of various diseases in adulthood, including hypertension and epilepsy. It has been reported that several organs show developmental retardation and functional deficiency in offspring of preeclamptic rats. However, the developmental and functional changes in brains of the offspring of preeclamptic rats remain unknown. Here, we established a preeclampsia-like rat model induced using Nω-nitro-L-arginine methyl ester (L-NAME) to analyze the developmental and functional changes in brains of the offspring. Body and brain weights were decreased in the L-NAME group at postnatal day 0 (P0). However, there were no significant differences between the L-NAME and control groups in brain and body weights at P56. Upon further analysis, we detected a deficiency in neurogenesis, but not in apoptosis, which contributed to the smaller brains of the offspring in the L-NAME group at P0. Additionally, we observed an increase in gliogenesis to compensate for the brain weights of the offspring at P56. Although the weight and laminar structure of the brains were essentially normal at P56, spatial learning and memory were severely impaired. We also found that adult hippocampal neurogenesis was disrupted in the offspring from preeclampsia-like rats, which may explain the cognitive deficiency. Moreover, qRT-PCR revealed a reduced expression of neurogenesis-related genes in the offspring. Overall, we have described the deleterious effects of preeclampsia on the brains of offspring, providing clues to the cellular and molecular mechanisms involved in this pathogenesis, which may aid in the development of therapeutic approaches.
子痫前期与婴儿发育迟缓以及成年后患各种疾病（包括高血压和癫痫）的风险增加有关。据报道，子痫前期大鼠的后代多个器官出现发育迟缓及功能缺陷。然而，子痫前期大鼠后代大脑的发育和功能变化仍不清楚。在此，我们建立了一种使用Nω-硝基-L-精氨酸甲酯（L-NAME）诱导的子痫前期样大鼠模型，以分析后代大脑的发育和功能变化。出生后第0天（P0），L-NAME组的体重和脑重降低。然而，在出生后第56天（P56），L-NAME组与对照组的脑重和体重没有显著差异。进一步分析发现，L-NAME组P0期后代脑体积较小是由于神经发生缺陷而非细胞凋亡所致。此外，我们观察到在P56期神经胶质生成增加以补偿后代的脑重。尽管在P56期大脑的重量和层状结构基本正常，但空间学习和记忆严重受损。我们还发现，子痫前期样大鼠后代的成年海马神经发生受到破坏，这可能解释了认知缺陷。此外，qRT-PCR显示后代中神经发生相关基因的表达降低。总体而言，我们描述了子痫前期对后代大脑的有害影响，为这一发病机制所涉及的细胞和分子机制提供了线索，这可能有助于开发治疗方法。
