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

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.

The novel testicular enrichment protein Cfap58 is required for Notch-associated ciliogenesis

“…The sperms and the cells that were grown on a coverslip coated with or without PDL were fixed in 4% paraformaldehyde (PFA) for 10 min at room temperature for cilia immunostaining or in methanol for 10 min at −20 • C for immunostaining of the centrosome and flagellar proteins. And then the sperms and cells were washed three times with PBS quickly at room temperature following standard immunofluorescence procedures [29]. The primary and secondary antibodies were listed in Supplementary Table S3.…”

Effects of placental growth factor deficiency on behavior, neuroanatomy, and cerebrovasculature of mice

“…These deficits were partially corrected through pravastatin administration (13,14), which has been shown to induce placental PGF expression in a similar model (42). Another model using N G -nitro-L-arginine methyl ester (L-NAME) to induce a PE-like phenotype in rats reported decreased offspring cortical thickness at postnatal day 0, as well as an increased number of glial cells and decreased hippocampal neurogenesis in adulthood (48). L-NAME model offspring showed impaired spatial memory and navigation in the water maze test (48,85) as well as impaired performance on a conditional discrimination Y-maze task (15).…”

“…Another model using N G -nitro-L-arginine methyl ester (L-NAME) to induce a PE-like phenotype in rats reported decreased offspring cortical thickness at postnatal day 0, as well as an increased number of glial cells and decreased hippocampal neurogenesis in adulthood (48). L-NAME model offspring showed impaired spatial memory and navigation in the water maze test (48,85) as well as impaired performance on a conditional discrimination Y-maze task (15). In these antiangiogenic models and in the Pgf Ϫ/Ϫ mouse, neuroanatomy of the hippocampus and associated structures appears to be vulnerable.…”

Distinct molecular processes in placentae involved in two major subtypes of preeclampsia

“…PE has significant consequences on fetal development and growth, often leading to perinatal and infant morbidity or mortality (Mol et al, 2016) and contributes preterm births (Davies et al, 2016) and ~15% cases of fetal growth restriction (FGR) (Mitani et al, 2009;Weiler et al, 2011). In the long term, PE affects brain development and functions of the offspring (Liu et al, 2016), leading to intellectual disability (Griffith et al, 2011), epilepsy (Wu et al, 2008, autism (Dachew et al, 2018b;Trosse et al, 2007;Walker et al, 2015) and schizophrenia (Dalman et al, 1999;Ursini et al, 2018).…”

“…[8][9][10] PE has significant consequences on fetal development and growth, often leading to perinatal and infant morbidity or mortality 1 and contributes preterm births 11 and ~15% cases of fetal growth restriction (FGR). 12,13 In the long term, PE affects brain development and functions of the offspring 14 , leading to intellectual disability, 15 epilepsy, 16 autism [17][18][19] and schizophrenia. 20,21 Since the symptoms of a pregnant woman with PE usually resolve after delivery and histopathological placental changes can be detected at that time, the placenta has been perceived as the root cause of PE.…”