Developmental and Functional Brain Impairment in Offspring from Preeclampsia-Like Rats.
Developmental and Functional Brain Impairment in Offspring from Preeclampsia-Like Rats.
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先兆子痫样大鼠后代的发育和功能性脑损伤
DOI：
10.1007/s12035-014-9060-7
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发表时间：
2016-03
影响因子：
5.1
通讯作者：
Li X
中科院分区：
文献类型：
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作者：
Liu X;Zhao W;Liu H;Kang Y;Ye C;Gu W;Hu R;Li X
先兆子痫与婴儿的发育迟缓有关，并与成年后各种疾病的风险增加有关，包括高血压和癫痫。已有研究表明，先兆子痫大鼠的子代出现多个器官发育迟缓和功能缺陷。然而，先兆子痫大鼠后代大脑的发育和功能变化仍然未知。本研究采用N ω-硝基-L-精氨酸甲酯（L-NAME）诱导的大鼠子痫前期模型，观察子代大鼠脑发育和功能的变化。胎龄0 d时，thel-NAME组体重和脑重均下降（P0）。然而，在P56时，thel-NAME组和对照组之间的脑重量和体重没有显著差异。在进一步分析后，我们检测到神经发生的缺陷，但不是在细胞凋亡，这有助于在P0时thel-NAME组的后代的较小的大脑。此外，我们观察到胶质细胞生成的增加，以补偿在P56的后代的脑重量。虽然在P56时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，在先兆子痫样大鼠的后代中，成年海马神经发生被破坏，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减少。总体而言，我们已经描述了先兆子痫对后代大脑的有害影响，提供了参与这种发病机制的细胞和分子机制的线索，这可能有助于治疗方法的发展。
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 usingNω-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 thel-NAME group at postnatal day 0 (P0). However, there were no significant differences between thel-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 thel-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.