Hippocampal Apoptosis Involved In Learning Deficits In The Offspring Exposed To Maternal High Sucrose Diets

Part1The effects of maternal high sucrose diets on braindevelopment and spatial cognition in the offspringObjective: To determine the effects of maternal high sucrose diets on braindevelopment and spatial cognition in the offspring.Methods: Pregnant rats were randomly divided into two groups. Control group (C)was provided with fresh water and standard rat food. High sucrose group (HS) wasgiven standard rat food and20%sucrose solution from gestational day1to day21.Maternal food and fluid intake were monitored. At gestational day21, maternal andfetal fasting plasma glucose levels as well as amniotic fluid glucose were examined;offspring were fed with standard food and fresh water after weaning, and1-month-oldand2-month-old fasting plasma glucose levels were examined too. Body and brainweight of fetus,1-and2-month-old rats were measured, and the ratio of brain to bodyweight were calculated. The Morris water maze (MWM) was used to assess the spatiallearning and memory ability of1-and2-month-old offspring.Results: There was no significant difference in maternal food intake, fluid intake,and body weight between the two groups. Plasma glucose in the high sucrose dietspregnant rats and offspring rats were significantly increased compared with that in thecontrol; No significant difference was found in amniotic fluid glucose. The body weightin HS offspring was increased. The brain weight in2-month-old offspring wassignificantly decreased in the HS group, and the ratio of brain to body weight at bothages was significantly lower than that of the control. Both ages of the HS offspringexhibited longer escape latencies and path length during testing in a hiddenplatform-learning phase. There was no significant difference in the time spent in thetarget quadrant and the number of target approaches between the two groups.Conclusion: Maternal over-intake of sucrose could influence brain developmentand affect the learning and navigational ability in the young offspring. Part2Thepro-apoptosiseffectsofmaternalhighsucrosedietsonhippocampusintheoffspringandtheassociatedsignalingpathwaysObjective: To determine the relationship between maternal high sucrose diets andhippocampal apoptosis in the offspring, and to investigate the possible signalingpathway involved.Methods: The2-month-old rat brains were cut into frozen sections and three brainregions were examined: CA1, CA2, and CA3of the hippocampus. To detect apoptoticnuclei, TUNEL staining was carried out. The numbers of positive cells wereautomatically counted. Expression of several apoptosis-related proteins (IGF-1, PI3K,Akt, p-Akt, caspase-3, Bcl-2, NR2B) were examined with Western blotting.Results: In HS offspring at two-month-old, the numbers of TUNEL-positive cellsin the area of CA1, CA2, and CA3in the hippocampus were significantly higher thanthat of the control. There was no difference in Bcl-2protein expression in thehippocampus between the control and HS offspring at two month of old, whilesignificant increase in activated caspase-3and NR2B was observed in HS group. TheIGF-I signaling elements, including IGF-I, PI3K, activated Akt (p-Akt), weresignificantly decreased in the HS offspring, while no differences were found in Akt.Conclusion: Maternal high sucrose diets may aggravate hippocampal apoptosis inthe offspring. Altered IGF-1/PI3K/Akt pathway elements in the hippocampus mightplay a critical role in the neuronal cell death.