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早年应激对成年大鼠行为和海马神经营养因子的影响

Effect of early life stress on behavior and neurotrophins of hippocampus in adult male rats

摘要目的 观察早年应激对雄性大鼠成年后行为和海马神经营养因子的影响.方法 将新生雄性大鼠随机分为早年应激组(12只)和对照组(12只).早年应激组大鼠出生后第2~14天每天与母鼠分离3h,第90天至第100天时用糖水偏好测验和旷场测验评估行为,采用逆转录-聚合酶链反应(RT-PCR)方法、Western blot方法检测海马神经营养因子(BDNF)和环磷酸腺苷(cAMP)反应元件结合蛋白(CREB)的mRNA及蛋白表达水平.结果 早年应激组的糖水偏好、旷场总行程、内围场地行程、平均速度、直立次数均少于对照组[(66.6±6.6)%、( 2793.33±945.66) cm、( 194.34±86.10) cm、(5.25±1.47)cm/s、(9.25 ±4.49)次比(80.9±3.5)%、(4888.00±1112.47) cm、(483.09 ±324.45) cm、(8.90±2.02) cm/s、(14.92 ±5.16)次,P<0.01].早年应激组的BDNF和CREB的mRNA及蛋白表达水平均显著低于对照组[(0.61±0.08)、(0.55 ±0.06)、(0.39±0.05)、(0.44±0.06)比(0.86±0.06)、(0.69 ±0.04)、(0.53±0.05)、(0.54±0.06),P<0.01].结论 生命早期应激可能改变成年后海马神经营养因子水平,导致成年后的行为改变,增加情感障碍的易感性.

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abstractsObjective To explore the effect of early life stress on behavior and neurotrophins of hippocampus in adult male rats.Methods Newborn male rats were randomly divided into early life stress group (n =12) and control group (n =12).The rats in early life stress group were deprived from their mother 3 h per day from postnatal day 2 to 14,and those in control group were given no treatment.When the animals grew up to 90-100 days,behaviors of these rats were assessed by sucrose preference test and open-field test.After behavior tests,rats were sacrificed and hippocampi were isolated.The levels of brainderived neurotrophic factor (BDNF)/cAMP responsive element-binding protein (CREB) mRNA and protein in the hippocampi were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Weston blotting.Results Behavior tests revealed that percentage of the sucrose preference,total distance,central total distance,mean velocity and erection in early life stress group were significantly less than those in control group [(66.6±6.6)%,(2793.33±945.66) cm,(194.34±86.10) cm,(5.25±1.47) cm/s,(9.25 ±4.49) times vs.(80.9 ±3.5)%,(4888.00±1112.47) cm,(483.09 ±324.45) cm,(8.90±2.02) cm/s,(14.92 ±5.16) times,P <0.01 ].Early life stress group showed a significant decrease in expression levels of BDNF/CREB mRNA and protein in hippocampi as compared with control group in their adulthood [(0.61 ±0.08),(0.55 ±0.06),(0.39 ±0.05),(0.44 ±0.06) vs.(0.86 ±0.06),(0.69 ±0.04),(0.53 ±0.05),(0.54 ±0.06),P<0.01].Conclusion Early life stress could alter neurotrophins of the hippocampi in adulthod,resulting in changes in behavior and susceptibility to affective disorders.

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