产前应激对子代大鼠学习记忆及焦虑行为的影响研究
Effects of Prenatal Stress on Anxiety of Behavior and Learning and Memory of Offspring Rats

作者: 蒋英虹 , 王义强 , 连 波 , 王 钢 , 孙宏伟 , 姜能志 , 孙 琳 :潍坊医学院心理学系,山东 潍坊;

关键词: 产前应激慢性轻度不可预计应激子代大鼠学习记忆焦虑Prenatal Stress Chronic Mild Unpredictable Stress (CUS) Offspring Rats Learning and Memory Anxiety

摘要:
目的:探讨母鼠妊娠后经历慢性轻度不可预计应激对其子代学习记忆和焦虑行为的影响。方法:应激组母鼠在怀孕时进行慢性应激干预,每日随机选取两种刺激(如湿笼、禁水食、束缚刺激等);而对照组母鼠不进行任何处理。子代大鼠于青春前期(28 d)和青春后期(49 d)进行Morris水迷宫试验;并在青春期后期(49 d)进行旷场实验。结果:对照组子鼠相比,应激组子鼠体重增长明显减缓(F = 13.098, *p < 0.05),在青春期中期(42 d~49 d)有较大的差异(42 d: F = 1.000, **P < 0.001;47 d: F = 0.173, **P < 0.001);青春前期(28 d)和青春后期(49 d)应激组子鼠在寻找平台的潜伏期较对照组没有明显差异,在青春期前期,对照组与应激组子鼠在时间上并没有显著差异(F = 0.246, P = 0.695),但是在路程上具差异显著具有统计学意义(F = 4.016, *P = 0.002);而在青春期后期,对照组与应激组子鼠在时间和路程上都差异不显著,无统计学意义;并且应激组子鼠的水平活动能力与垂直活动能力明显少于对照组子鼠(穿格数:F = 0.1543,**P < 0.001;直立次数:F = 1.764,P = 0.002;梳理次数:F = 1.287,**P < 0.001)。结论:产前应激会损伤子代大鼠的记忆认知的发展并导致幼儿期及青春期学习记忆能力的减退,易引发焦虑情绪和行为。

Abstract: Objective: To determine the effect of prenatal chronic unpredictable mild stress (CUS) during the pregnancy on the behavior parameters of learning and memory and anxiety of the rat offspring. Methods: The prenatal CUS model was adopted. During pregnancy to fertility, the mothers of CUS group underwent two stimuli daily randomly (such as wet, 45˚ inclined cage, cage ban water feed, bound to stimulate, etc.); While the mothers of control group didn’t deal with any processing. The offspring rats from each group were examined in Morris Water Maze at preadolescence (28 d) and postpubescence (49 d), and examined the spontaneous behavior and anxiety behavior by the open-field test at postpubescence (49 d). Results: CUS influences on growth of rat body weight (F = 13.098, *P < 0.05), in the middle of the puberty (42 d - 49 d), have bigger difference (42 d: F = 1.000, **P < 0.001; 47 d: F = 0.173, **P < 0.001), and there was no significant difference in the search for the platform of the incubation period between the offspring rats of stress group and offspring rats of control group offspring at preadolescence (28 d) and postpubescence (49 d) (F = 0.246, P = 0.695), while there was also a difference in the search strategy of straight and random patterns in postpubescence (49 d) offspring rats (F = 4.016, *P < 0.05). The horizontal and vertical mobility of the offspring rats of stress group was less than the offspring rats of control group, the difference is statistically significant (Crossing: F = 0.1543, **P < 0.001; Upright: F = 1.764, P = 0.002; Comb: F = 1.287, **P < 0.001). Conclusion: Prenatal stress will affect the development of the offspring rats memory cognitive, damage the ability of learning and memory of early childhood and adolescence, and easy to cause anxiety.

文章引用: 蒋英虹 , 王义强 , 连 波 , 王 钢 , 孙宏伟 , 姜能志 , 孙 琳 (2016) 产前应激对子代大鼠学习记忆及焦虑行为的影响研究。 国际神经精神科学杂志, 5, 27-34. doi: 10.12677/IJPN.2016.52005

参考文献

[1] Conrad, C.D. (2010) A Critical Review of Chronic Stress Effects on Spatial Learning and Memory. Progress in Neu-ro-Psychopharmacology and Biological Psychiatry, 34, 742-755.
http://dx.doi.org/10.1016/j.pnpbp.2009.11.003

[2] Kofman, O. (2002) The Role of Prenatal Stress in the Etiology of Developmental Behavioural Disorders. Neuroscience & Biobehavioral Reviews, 26, 457-470.
http://dx.doi.org/10.1016/S0149-7634(02)00015-5

[3] Weinstock, M. (2005) The Potential Influence of Maternal Stress Hormones on Development and Mental Health of the Offspring. Brain, Behavior, and Immunity, 19, 296-308.
http://dx.doi.org/10.1016/j.bbi.2004.09.006

[4] King, S., Mancini-Marïe, A., Brunet, A., Walker, E., Meaney, M.J. and Laplante, D.P. (2009) Prenatal Maternal Stress from a Natural Disaster Predicts Dermatoglyphic Asymmetry in Humans. Development and Psychopathology, 21, 343- 353.
http://dx.doi.org/10.1017/S0954579409000364

[5] Wadhwa, P.D., Sandman, C.A. and Garite, T.J. (2001) The Neurobiology of Stress in Human Pregnancy: Implications for Prematurity and Development of the Fetal Central Nervous System. Progress in Brain Research, 133, 131-142.
http://dx.doi.org/10.1016/S0079-6123(01)33010-8

[6] Kapoor, A., Dunn, E., Kostaki, A., Andrews, M.H. and Matthews, S.G. (2006) Fetal Programming of Hypothalamo- Pituitary-Adrenal Function: Prenatal Stress and Glucocorticoids. The Journal of Physiology, 572, 31-44.
http://dx.doi.org/10.1113/jphysiol.2006.105254

[7] 武捷, 宋天保, 张征宇, 等. 产前应激对子代大鼠学习记忆的影响[J]. 西安交通大学学报(医学版), 2003, 24(6): 572-574.

[8] Akil, H. (2005) Stressed and Depressed. Nature Medicine, 11, 116 -118.
http://dx.doi.org/10.1038/nm0205-116

[9] Paul, W. (1997) Validity, Reliability and Utility of the Chronic Mild Stress Model of Depression: A 10-Year Review and Evaluation. Psychopharmacology (Berl), 134, 319-329.
http://dx.doi.org/10.1007/s002130050456

[10] Anisman, H. and Matheson, K. (2005) Stress, Depression, and Anhedonia: Caveats Concerning Animal Models. science & Biobehavioral Reviews, 29, 525-546.
http://dx.doi.org/10.1016/j.neubiorev.2005.03.007

[11] Liu, Y.X., Hu, J.H. and Zhu, Q.G. (2008) A New Method to Make Water for the Morris Water Maze. Laboratory Animal and Comparative Medicine, 28, 243-245.

[12] Wang, Z., Hu, S.Y., Song, C.H., Peng, G.J. and Huang, C.Y. (2004) Effect of Baisong Tablet on Behavior and CORT, ACTH in Plasma of Chronic Stress Depression Rats. Chinese Journal of Clinical Psychology, 12, 14-17.

[13] Eldridge, J.C., Wetzel, L.T. and Tyrey, L. (1999) Estrous Cycle Patterns of Sprague-Dawley Rats during Acute and Chronic Atrazine Administration. Re-productive Toxicology, 13, 491-499.
http://dx.doi.org/10.1016/S0890-6238(99)00056-8

[14] Cryan, J.F., Mombereau, C. and Vassout, A. (2005) The Tail Suspension Test as a Model for Assessing Antidepressant Activity: Review of Pharmacological and Genetic Studies in Mice. Neuroscience & Biobehavioral Reviews, 29, 571- 625.
http://dx.doi.org/10.1016/j.neubiorev.2005.03.009

[15] Nilsson, C., Jennische, E., Ho, H.P., Eriksson, E., Björntorp, P. and Holmäng, A. (2002) Increased Insulin Sensitivity and Decreased Body Weight in Female Rats After Postnatal Corticosterone Exposure. European Journal of Endocrinology, 146, 847-854.
http://dx.doi.org/10.1530/eje.0.1460847

[16] Kapoor, A., Kostaki, A., Janus, C. and Matthews, SG. (2009) The Effects of Prenatal Stress on Learning in Adult Offsring Is Dependent on the Timing of the Stressor. Behavioural Brain Research, 197, 144-149.
http://dx.doi.org/10.1016/j.bbr.2008.08.018

[17] Morris, R. (1984) Developments of a Water-Maze Procedure for Studying Spatial Learning in the Rat. Journal of Neuroscience Methods, 11, 47-60.
http://dx.doi.org/10.1016/0165-0270(84)90007-4

[18] Jaffard, R.J., Bontempi, B. and Menzaghi, F. (2001) Theoretical and Practical Considerations for the Evaluation of Learning and Memory in Mice. Methods of Behavior Analysis in Neuroscience, FL, 301-329.

[19] Sun, L., Lam, W.P., Wong, Y.W., Lam, L.H., Tang, H.C., Wai, M.S., et al. (2012) Permanent Deficits in Brain Functions Caused by Long-Term Ketamine Treatment in Mice. Human & Experimental Toxicology, 30, 1287-1296.
http://dx.doi.org/10.1177/0960327110388958

[20] Cuadrado-Tejedor, M., Ricobaraza, A., Del, R.J., Frechilla, D., Franco, R., Pérez-Mediavilla, A., et al. (2011) Chronic Mild Stress in Mice Promotes Cognitive Impairment and CDK5-Dependent Tau Hyperphosphorylation. Behavioural Brain Research, 220, 338-343.
http://dx.doi.org/10.1016/j.bbr.2011.01.005

[21] Conrad, C.D. (2010) A Critical Review of Chronic Stress Effects on Spatial Learning and Memory. Progress in Neuro- Psychopharmacology and Biological Psychiatry, 34, 742-755.
http://dx.doi.org/10.1016/j.pnpbp.2009.11.003

[22] Lemaire, V., Koehl, M., Le, M.M. and Abrous, D.N. (2009) Prenatal Stress Produces Learning Deficits Associated with an Inhibition of Neurogenesis in the Hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 7, 11032-11037.

[23] 王庆雄, 静进, 蔡小梅, 等. 非言语型学习障碍儿童视觉空间认知特征与行为问题[J]. 中国心理卫生杂志, 2005, 19(1): 15-18.

[24] 王维刚, 刘震泽, 吴文婷, 等. 小鼠动物实验方法系列专题(七)旷场实验在小鼠行为分析中的应用[J]. 中国细胞生物学学报, 2011, 33(11): 1191-1196.

[25] Casu, M.A., Pisu, C., Sanna, A., Tambaro, S., Spada, G.P., Mongeau, R., et al. (2005) Effect of 9-Tetrahydrocannabinol on Phosphorylated CREB in Rat Cerebellum: An Immunohistochemical Study. Brain Research, 1048, 41-47.
http://dx.doi.org/10.1016/j.brainres.2005.04.053

[26] Vallée, M., Mayo, W., Dellu, F., Le, MM., Simon, H. and Maccari, S. (1997) Prenatal Stress Induces High Anxiety and Postnatal Handing Induces Low Anxiety in Adult Offspring: Correlation with Stress-Induced Corticosterone Secretion. The Journal of Neuroscience, 17, 2626-2636.

[27] Martínez-Téllez, R.I., Hernández-Torres, E., Gamboa, C. and Flores, G. (2009) Prenatal Stress Alters Spine Density and Dendritic Length of Nucleus Accumbens and Hippocampus Neurons in Rat Offspring. Synapse, 63, 794-804.
http://dx.doi.org/10.1002/syn.20664

[28] 王建醒, 周丽, 徐华锋, 等. 慢性应激大鼠抑郁模型的建立及其评价[J]. 齐齐哈尔医学院学报, 2006, 27(6): 644-646.

分享
Top