孕前慢性应激对母鼠及其子代行为学和海马神经元再生的影响

Effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the postpartum behavior and neurobiology of themselves and their progency

目的 通过母鼠孕前慢性应激抑郁模型探讨母鼠及其子代行为学和海马区神经元再生的变化.方法 取2月龄性成熟期的雌性Sprague dawley （SD）大鼠,21 d慢性应激之后,使大鼠生产繁殖,分别取哺乳后母鼠、2月龄的子鼠进行行为学实验,取2月龄子鼠脑组织制作冰冻切片,用BrdU标记法检测子代鼠大脑海马神经前体细胞的增殖.结果 ①开场实验：母鼠哺乳期过后应激＋妊娠组[（720.52±238.99）cm]、应激＋非妊娠组[（995.62±191.77）cm]、非应激＋妊娠组[（464.95±210.11） cm]和非应激＋非妊娠组[（740.76±281.48）cm]各组总路程相比差异有统计学意义（P＜0.05）.2月龄子鼠应激＋妊娠组雌鼠总路程[（1281.10±247.89） cm]、周边路程[（1153.20±238.19）cm]与雄鼠的[（1074.70±263.35）cm]、[（957.28±282.94）cm]相比增加（P＜0.05）.②蔗糖水消耗实验：母鼠哺乳后,应激＋妊娠组蔗糖水消耗量（13.00±3.46）g和蔗糖水消耗百分比[（87.00±9.01）％]多于应激＋非妊娠组[（8.13±3.36）g、（79.06±6.45）％]（P＜0.05）；非应激＋非妊娠组蔗糖水消耗量[（12.43±3.31）g]和蔗糖水消耗百分比[（86.90±5.80）％]多于应激＋非妊娠组[（8.13±3.36）g、（79.06±6.45）％,P＜0.05]；非应激＋妊娠组糖水消耗量[（14.71±4.39）g]和蔗糖水消耗百分比[（91.54±1.89）％]明显多于应激＋非妊娠组[（8.13±3.36）g、（79.06±6.45）％,P＜0.01].③免疫组化实验应激组雌鼠[（1.18±0.37）个]、应激组雄鼠[（1.24±0.41）个]、非应激组雌鼠[（1.38±0.47）个]、非应激组雄鼠[（1.41±0.35）个]4组相比较脑组织单位海马齿状回面积内BrdU阳性细胞数差异没有统计学意义（P＞0.05）.结论 ①孕前应激可致母鼠的焦虑和抑郁样行为,并且哺乳能够减弱孕前应激所致的焦虑和抑郁样行为.②未发现孕前应激对2月龄子鼠的行为学和海马神经细胞再生产生明显的影响,但在焦虑样行为中会表现出雌雄差异.

Objective To determine the effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behavior and neurobiology of the mother and their offspring.Methods Two-month Virgin female Sprague-Dawley（SD） rats were applied to study.Females were housed with sexually experienced males （ratio 3：1） for propagation after 21-day chronic unpredictable stress.The behaviors of rats and their two-month-offspring were tested.The two-month rats were injected intraperitoneally with BrdU,then the brains were removed and 20 μm frozen sections were used to detect the neurogenesis of hippocampus.Results 1.Open field test：after lactation,CUS ＋ Pre group （（720.52 ± 238.99） cm）,CUS group （（995.62 ± 191.77） cm）,CON group （（464.95 ±210.11）cm） and CON ＋ Pre group（（740.76 ± 281.48）cm） had statistic difference in total distance（P 〈 0.05）.The total distance（（1281.10 ±247.89）cm） and border distance（（1153.20 ±238.19）cm） in female two-monthprogeny were higher than these in male two-month-progeny （（1074.70 ± 263.35） cm,（957.28 ± 82.94） cm） in CUS ＋ Pre group （P 〈 0.05）.2.Sucrose consumption test：after lactation,the sucrose intake （（13.00 ± 3.46） g）and sucrose consumption percentage（（87.00 ±9.01）%） in CUS ＋ Pre group were higher than that in CUS group （（8.13 ± 3.36） g,（79.06 ± 6.45） %,P 〈 0.05）.The sucrose intake （（12.43 ± 3.31） g） and sucrose consumption percentage（（86.90 ± 5.80）%） in CON group were higher than that in CUS group （（8.13 ± 3.36） g,（79.06 ± 6.45） %,P 〈 0.05）.The sucrose intake （（14.71 ± 4.39） g） and sucrose consumption percentage （（91.54 ± 1.89） %） in CON ＋ Pre group were significantly higher than those in CUS group （（8.13 ± 3.36） g,（79.06 ± 6.45） %） （P 〈 0.01）.3.Immunohistochemistry：there was no statistic difference on the new neuron in dentate gyrus of hippocampus in both female and male two-month-progeny of CUS group and CON group（（1.18 ±0.37） cells,（1.24 ± 0.41） cells,（1.38 ± 0.47） cells,（1.41 ± 0.35） cells） （P 〉 0.05）.Conclusion The 21d CUS before pregnancy induce the anxiety-like behavior and depressive-like behavior in maternal rats,and lactation can attenuate influence of stress to protect maternal rats.There is no effect on the behavior and cell proliferation of hippocampus in adult progeny by chronic unpredictable stress exposure before pregnancy.However,there is the difference of anxiety-like behavior in both female and male two-month-progeny.