Developmental and Functional Brain Impairment in Offspring from Preeclampsia-Like Rats.

Xueyuan Liu,Yaoyue Kang,Haiyan Liu,Chen Ye,Xiaotian Li,Rong Hu,Weirong Gu,Wenlong Zhao

doi:10.1007/s12035-014-9060-7

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-014-9060-7) contains supplementary material, which is available to authorized users.

Highlights

Preeclampsia is associated with increased morbidity and mortality, and epidemiologic evidence has shown that infants from preeclamptic mothers are susceptible to respiratory distress syndrome, hypertension, stroke and/or epilepsy in adult life [1,2,3]
We found that the offspring in the L-NAME group exhibited smaller brains at postnatal day 0 (P0), but they were not significantly different at P56 compared with the control group (Fig. 2a, b)
Statistical analysis was performed with the Mann-Whitney test. c Ratio of brain weight to body weight at P0 and P56 in the L-NAME and control groups. d Coronal sections of P0 and P56 rat brains stained with hematoxylin and eosin. e Statistical results for cortex thickness in P0 and P56 rat pups in the L-NAME and control groups

Summary

Introduction

Preeclampsia is associated with increased morbidity and mortality, and epidemiologic evidence has shown that infants from preeclamptic mothers are susceptible to respiratory distress syndrome, hypertension, stroke and/or epilepsy in adult life [1,2,3]. It is necessary to establish preeclamptic animal models for further investigation of the adverse effects on the offspring of preeclamptic pregnancies. Some studies have focused on the development and function of the lungs, kidneys, and vascular endothelium of infants from preeclamptic mothers or offspring from preeclampsia animal models [6,7,8]. There are only a few scattered studies concerning the developmental and functional changes in the nervous systems of offspring from preeclampsia pregnancies in humans and rats [12, 13]. The aims of this study were to investigate whether preeclampsia disrupts the development and function of the brain and to explore the mechanisms underlying these perturbations in the offspring of preeclamptic dams

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Conclusion