To Investigate The Mechanism Of Induced Learning And Memory Impact In The Rat Offsprings Of Prenatal Stress Based On The Change Of HPA Axis Regulation And CA1 Hippocampal Dendritic Spines

OBJECTIVETo build the model of prenatal stress,in order to reveal the possible molecular mechanisms on the influence of pregnant rats prenatal stress to learning and memory of their offspring rats. Through examining the learning and memory of the developing rat offspring, detecting the basal levels of corticosterone(COR) and adrenocorticotropic hormone(ACTH), comparing density and morphology of the CA1 hippocampal dendritic spines.METHODSPregnant females were individually restrained in the diameter of 6 cm length adjustable ventilation transparent plastic bottles for 45 min three times a day in the last week of pregnancy from day 14 until delivery. Control pregnant females were left undisturbed in their home cages. The rat offsprings were randomly assigned to prenatal stress(PS) or control(C) groups.Males and females were kept for the study separately.We examined the learning and memory of the developing rat offspring in the Morris water maze.The basal plasma levels of COR and ACTH was detected by using radioimmunoassay. We used the Golgi-Cox method to stain brain tissue,then used an optical microscope to observe density and morphology of the CA1 hippocampal dendritic spines and took photograph.To count the number of dendritic spines through the MATLAB software.RESULTS1 The Morris Water MazeThe place navigation task As the training days adding,the escape latency(EL) of each group gradually shorten, but always show certain regularity.The EL to find the platform by the control group was significantly less than that observed for the PS group in female rat offsprings(F=4.533,P<0.05),the difference is statistically significant in the 5th day(t=2.788,P<0.05).The escape latency(EL) to find the platform by the control group was significantly less than that observed for the PS group in male rat offsprings(F=6.101,P<0.01),the difference is statistically significant in the 2th day(t=3.051,P<0.01).The spatial probe trial The time spent in target quadrant as a percentage of total time for the PS group in female rat offsprings is(29.98±5.80)%,and(32.90±7.70)% for the Control group. Differences among those were not significant. The time spent in target quadrant as a percentage of total time for the PS group in male rat offsprings is(29.76±5.85)%,and(30.92±6.09)%for the Control group. Differences among those were not significant.2 The basal plasma levels of COR and ACTHThe basal plasma levels of COR for the PS group in female rat offsprings is(28.77±2.49)mg/L, and(24.01±3.26)mg/L for the Control group, the difference is statistically significant(t=3.658,P<0.01). The basal plasma levels of COR for the PS group in male rat offsprings is(69.43±15.84)ng/L, and(51.65±18.34)ng/L for the Control group, the difference is statistically significant(t=2.319,P<0.05).3 The Golgi–Cox stainingThe density of the CA1 hippocampal dendritic in PS group is(7.75±0.76)/10μm,and(7.75±0.76) in Control group, the difference is statistically significant(t=-3.072,P<0.01).A Simplified pattern was observed in the CA1 hippocampal dendritic spines of the PS group,showed up as a less extent of dendritic arborization and the density was significantly lower than that observed for the control group.CONCLUSIONS1. The prenatal chronic stress can damage the learning ability of rat offsprings, not obvious influence on memory ability.2. The prenatal chronic stress can damage the hypothalamus- pituitary- adrenal(HPA) axis function of rat offsprings.3. The reprogramming of HPA axis function influence the CA1 area vertebral neuron dendritic growth, showed up as a less extent of dendritic arborization and the density was significantly lower.It may be mechanism of cognitive alterations following prenatal chronic stress.