Abstract: Objective To investigate the effects of neonatal maternal separation on behavior and mental problems in rat,and to explore the effects of maternal separation on oxytocin and related molecules expression and neurodevelopment in rats. Methods Neonatal SD rats were randomly divided into control group and neonatal maternal separation group(NMS group). Rats in NMS group were separated from their mothers for 2 hours from 1 to 14 days after birth. Behavioral tests were performed at the age of 6 weeks old,including open-field tests,three-chambered tests,elevated-plus maze and forced-swimming tests. The expression of CD38 protein in rat hypothalamus was detected by Western blot. The serum OXT level was detected by ELISA. Results In the NMS rats,the time[control vs. NMS:(29. 19±3. 55)s,(55. 90±4. 03)s,P<0. 001]and frequency of self-grooming(6. 67±0. 74 vs. 9. 53±0. 73,P<0. 05) increased significantly,suggesting an increase of stereotyped behavior. And the interaction time with unfamiliar rats was decreased [(350. 40±41. 25)s,(260. 30±33. 43)s,P<0. 05],suggesting that social function of NMS rats was impaired; the decreased time spent in open-arms [(78. 15±20. 95)s vs. (36. 45±5. 35)s,P<0. 05] of elevated-plus-maze in the central area of the open-field [(153. 7±34. 41)s vs. (13. 84±4. 80)s,P<0. 01)] and the increasing frequency of defecation(1. 72±0. 24,3. 25±0. 26,P<0. 001)suggesting the increased anxiety-like behavior of rats; the immobility latency[(59. 02±8. 64)s,(33. 97±5. 87)s,P<0. 05]and the shortened total struggling time in the forced swimming test,suggesting the depressive behavior of NMS rats. In addition,the expression of hypothalamic CD38(P＜0. 01) protein and the serum OXT level(P＜0. 05) were significantly lower in NMS rats. Conclusions 1) Maternal and child isolation in early life may lead to autism-like behavior,anxiety and depression-like behavior in adult rats. 2) Maternal-infant separation may reduce the release of OXT by reducing the expression of CD38 protein in hypothalami,thereby leading to abnormal behaviors.

Key words: neonatal maternal separation, behavior development, oxytocin, CD38

摘要： 目的 探讨大鼠生命早期母婴分离对成年期异常行为、情绪问题及体内催产素及相关分子表达的影响。方法 将新生SD大鼠随机分为对照组和新生期母婴分离组(NMS组),NMS 组新生鼠生后第 1~14 天每天与母鼠分离2 h,6周龄进行行为学测试,包括旷场测试、三厢社交测试、高架十字迷宫和强迫游泳测试。Western blot方法检测大鼠下丘脑组织CD38蛋白表达水平,ELISA检测大鼠血清OXT水平。结果 与对照组相比,NMS大鼠成年后自身梳理时间[(29.19±3.55)s,(55.90±4.03)s,P<0.001]和次数(6.67±0.74,9.53±0.73,P<0.05)均显著增加,提示刻板行为增加;与同伴互动时间减少[(350.40±41.25)s,(260.30±33.43)s, P<0.05],提示社交功能受损;对新环境的探索时长[高架开放臂:(78.15±20.95)s vs.(36.45±5.35)s,P<0.05;旷场中央区:(153.70±34.41)s vs.(13.84±4.80)s,P<0.01]减短、排便次数增多(1.72±0.24,3.25±0.26,P<0.001),提示焦虑样行为增加;强迫游泳试验中首次不动潜伏期缩短[(59.02±8.64)s,(33.97±5.87)s,P<0.05],提示抑郁样行为加重。此外,NMS大鼠下丘脑CD38蛋白表达水平(P<0.01)、血清OXT含量(P<0.05)明显降低。结论 1)生命早期母婴分离可能导致大鼠成年后出现孤独症样行为,焦虑、抑郁样行为。2)母婴分离可能通过降低大鼠下丘脑组织中CD38蛋白表达,进一步引起OXT释放减少,导致相关行为异常。

关键词: 新生期母婴分离, 行为学, 催产素, CD38