母鼠孕期及哺乳期高脂饮食对成年子代行为及学习记忆的影响

The effects of high-fat diet during pregnancy and lactation on the behaviors and learning memory in adult male offspring

目的 观察母鼠高脂饮食对子代成年后行为及学习记忆能力的影响,并初步探讨可能的机制.方法 孕期及哺乳期SD母鼠喂食高脂（high fat diet,HF）或标准饲料（normal diet,ND）,子代雄性大鼠断奶后喂食标准饲料至120 d.随后母鼠喂食HF或ND的子代大鼠接受14 d正常饲养或慢性不可预见性应激（chronic unpredictable mild stress,CUMS）,分为ND组,ND＋ CUMS组,HF组以及HF＋CUMS组（各9只）;采用旷场实验、糖水偏好实验与强迫游泳实验评价各组抑郁样行为,采用Morris水迷宫评价学习记忆能力.另外两组正常饲养的ND及HF组（各8只）行心导管置管,基础及应激状态（束缚,1h）下采集血液,检测促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）及皮质酮（corticosterone,CORT）水平.结果 （1） HF组较ND组大鼠糖水偏好度降低（P＜0.05）;与ND组比较,ND＋CUMS组出现明显抑郁样行为.HF＋CUMS组旷场实验的垂直运动得分、糖水偏好度[分别为（11.36±8.25）分,（0.63±0.04）]低于ND＋CUMS组[分别为（17.12±7.54）分,（0.73±0.05）],而HF＋CUMS组游泳不动时间[（33.16±6.35）s]高于ND＋CUMS组[（25.74±7.31）s],均差异有统计学意义（P＜0.05）.（2） Morris水迷宫实验中,HF组经过平台次数少于ND组（P＜0.05）;与ND＋CUMS组比较,HF＋CUMS组目标象限时间、有效区域停留时间以及经过平台次数均显著减少（P＜0.05）.（3）HF与ND两组大鼠血ACTH及CORT基础水平无明显差异（P＞0.05）;1 h束缚中,激素水平均明显上升,但两组之间差异无统计学意义（P＞0.05）.束缚结束3h内多个时间点,HF组ACTH及CORT水平均高于ND组（P＜0.05）.结论 孕期及哺乳期（即子代生命发育早期）母体高脂饮食增加成年子代大鼠正常情况下抑郁样行为易感性及应激状态下的严重程度,并降低其学习记忆能力,这可能与应激状态下下丘脑-垂体-肾上腺轴活性改变相关.

Objective To investigate the effects of high-fat feeding during pregnancy and lactation on the behaviors and learning memory in adult male offspring,as well as explore its possible mechanisms.Methods Female SD rats were exposed to either high fat diet （HF） or normal diet （ND） during pregnancy and lactation period.From weaning,all male offspring were fed with ND until 120-day.The offspring whose mothers were fed with HF or ND received 14 d chronic unpredictable mild stress （CUMS） or normal circumstance,and being divided into ND group,ND＋CUMS group,HF group and HF＋CUMS group（9 rats in each group）.The Open-field test,sucrose preference test and forced swimming test were used to evaluate the depressive-like behaviors,and Morris water maze test was employed to assess the learning and memory ability.Moreover,blood samples were taken via chronically implanted cardiac catheters for measurement of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） levels in another set of DN group and HF group with normal circumstance during baseline and restraint stress （1 h）.Results （1） Compared with the ND group,the sucrose preference in the HF group were decreased （P〈0.05）.Compared with ND group,ND ＋CUMS group showed more serious depressive-like behavior.Vertical score in open-field test （11.36±8.25） and sucrose preference（0.63±0.04） of HF＋CUMS group,were lower than those of the ND＋CUMS group （（17.12±7.54）,（0.73±0.05）,respectively）.The immobility time in forced swimming test of HF＋CUMS group （（33.16±6.35）s） were longer than that of ND＋CUMS group （（25.74±7.31） s）.（2） In Morris water maze test,the crossing platform times of the HF group was less than those of the HF group.Compared with ND＋CUMS group,the target quadrant time,effective area residence time and crossing platform times of HF＋CUMS group were decreased significantly （P〈0.05）.（3）There was no differences in basal ACTH and CORT between ND group and HF group （P〉0.05）.Both ND group and HF group exhibited significantly elevated levels of plasma ACHT and CORT during restraint,but without significant difference between these two groups （P〉 0.05）.Within 3 h after restraint,the HF group showed significant increase of ACTH and CORT compared with ND group（P〈0.05）.Conclusion As one kind of distress in early life,high-fat geeding through pregnancy and lactation increase the susceptibility and severity of depressive-like behaviors in adult offspring,as well as reducing the learning and memory ability,and the activity of hypothalamic-pituitary-adrenal axis activity during stress may contribute to the changes.