Effects And Mechanisms Of Prenatal High Sucrose Intake On Learning And Memory Of Aged Rat Offspring

Objectives: The present study investigated long-term impact of prenatal high sucrose(HS)diets on cognitive capabilities in aged rat offspringMethods: Pregnant Sprague-Dawley rats(250-280g)were obtained from Soochow University Animal Center.Rats were housed in a climate-controlled light-regulated facility with 12:12 h day-night cycles and allowed to free access to food and water.Pregnant rats were randomly divided into two groups(N=11 each group).From gestational 1 to 21 day,one group was fed with 20% sucrose solution and the other was fed with fresh tap water(C).Both groups were provided with the same standard rat food containing 39.1% carbohydrates,19.3% protein,4.0% fat,0.6% NaCl,1.00% calcium,0.70% phosphate and 0.68% potassium(Slaccas,Shanghai,China).During pregnancy,there was no difference in daily fluid intake(36.2±1.4ml/day versus 36.3±1.5ml/day).After delivery,all rats were provided with fresh tap water.An average litter size was 9-14.After weaning,male offspring from both groups(n=1 from each dam)were randomly selected and raised with standard food until 18 month old.Body weight and brain weight,plasma glucose and insulin concentration in aged offspring were measured.The levels of the Thiobarbituricacid reactive substances(TBARS)and the activity of catalase in the hippocampus were detected by Assay Kit.The mRNA abundance and protein abundance were detected by RT-PCR and Western-blot.Results: The fasting plasma glucose concentration did not differ between the control and HS groups.However,the fasting plasma insulin and insulin resistance index values were significantly increased in HS offspring that showed abnormal glucose tolerance test.HS offspring exhibited increased escape latency and swimming path length to the platform,and reduced time in the target quadrant and the number of crossing the platform,as compared with the control group.The expression of Grin2b/NR2 B,Wnt2,Wnt3 a and active form of ?-catenin protein were decreased,and Dickkopf-related protein 1 was increased in the HS group.In addition,the levels of lipid peroxidation biomarker thiobarbituricacid reactive substance,nicotinamide adenine dinucleotide phosphate oxidases 2 and superoxide dismutase 1 were significantly increased,and the activity of catalase was decreased in the hippocampus in the HS group.Conclusions: The results demonstrate that prenatal HS-induced metabolic changes cause cognitive deficits in aged rat offspring,probably due to altered N-methyl-D-aspartate receptors/Wnt signaling and oxidative stress in the hippocampus.