The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus

BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

IGF2 expression in blood is not associated with its imprinting status in healthy pregnant Chinese women

Loss of Imprinting (LOI) of IGF2 and over-expressed IGF2 are associated with tumorigenesis. Our previous epidemiological study found a relatively high frequency of IGF2 LOI in healthy mid-gestation pregnant women. The aim of this study is to determine whether the expression of IGF2 is associated with its imprinting status in healthy Chinese pregnant women. The IGF2 imprinting status of 300 pregnant women was analyzed. 20 cases of IGF2 LOI and 20 cases of IGF2 retention of imprinting (ROI) were selected randomly for IGF2 expression analysis. The expression pattern of IGF2 between the group with IGF2 ROI and group with IGF2 LOI in healthy Chinese pregnant women was evaluated by real time PCR and western blot. The result showed no significant differences between IGF2 ROI and LOI groups in mRNA and protein levels. These results imply that IGF2 imprinting status has no obvious impact on its expression. There may be some unknown important factors other than imprinting status driving IGF2 expression.

Insulin-like growth factors-I and -II and insulin-like growth factor binding protein-1 during normal pregnancy: pattern of secretion and correlation with other placental hormones.

OBJECTIVES: To describe pattern of secretion of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-1 and their correlation with each other and major placental hormones during normal pregnancy. DESIGN: Longitudinal study. SETTING: Academic Institutions and a Tertiary Care Maternity Hospital. PARTICIPANTS: Healthy women with singleton uncomplicated pregnancies (N = 35). MEASUREMENTS: Serum levels of IGF-I, IGF-II, IGFBP-1, chorionic gonadotrophin (HCG), placental lactogen (HPL), prolactin, oestradiol and progesterone were studied thrice during the antenatal period and within 24 h of delivery. RESULTS: IGF-I, IGFBP-1, HPL, prolactin, oestradiol and progesterone increased and HCG decreased significantly with advancing gestation (Repeated measures ANOVA: P < 0.01 to 0.0001). IGF-II levels were not significantly affected by period of gestation. Significant negative correlations (multiple regression analysis) were seen between IGFBP-1 and prolactin at 28 +/- 2 (P = 0.0226) and 36 +/- 2 (P = 0.0417) weeks of amenorrhoea (WOA) and between oestradiol and IGF-II at 36 +/- 2 WOA (P = 0.037). Prolactin and IGF-I at 14 +/- 2 WOA (P = 0.0225) and progesterone and IGFBP-1 at 28 +/- 2 WOA (P = 0.0216) correlated positively. CONCLUSIONS: Maternal IGF-I and IGFBP-1 but not IGF-II significantly increase as pregnancy advances. Components of the IGF system regulate or are affected by some of the placental hormones and the effects vary with the period of gestation.

Growth promotion of HepG2 hepatoma cells by antisense-mediated knockdown of glypican-3 is independent of insulin-like growth factor 2 signaling

Glypican-3 (GPC3) encodes a cell-surface heparan-sulfate proteoglycan and its expression is frequently silenced in ovarian cancer, mesotheliomas, and breast cancer cell lines and ectopic expression of GPC3 inhibited the growth of these cells, suggesting that GPC3 plays a negative role in cell proliferation. In contrast, up-regulation of GPC3 is often observed in hepatoma, neuroblastoma, and Wilms' tumor. Whether GPC3 plays the same growth inhibitory role in these tumors remains to be studied. Here we report that antisense-mediated knockdown of GPC3 in the HepG2 hepatoma cells significantly promotes the growth of hepatoma cells. In addition, we show that this growth promotion is independent of insulin-like growth factor 2 (IGF2) signaling. Our data suggest that GPC3 plays a growth-suppressing role in hepatoma and provide cell biological evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by downregulating IGF2.