中晚期孕期束缚应激对子代下丘脑多巴胺能神经元发育的影响
Effects of prenatal stress on the development of dopaminergic neurons in the hypothalamus of offspring
目的 研究中晚期孕期束缚应激对子代下丘脑多巴胺能神经元发育的影响。 方法 使用怀孕SD大鼠，实验组在孕期第15~21 d进行束缚应激，对照组则不受任何干扰。子代大鼠出生的当天为出生后的第0 天。在子代大鼠出生后的第1天（P1），第7天（P7）和第30天（P30）,分别测子代大鼠的体重，通过免疫组织化学染色和Western Blotting，观察和比较下丘脑内合成多巴胺的关键酶酪氨酸羟化酶（TH）染色像素密度及TH蛋白水平变化。 结果 与正常对照组相比，中晚期孕期束缚应激子代大鼠在P1体重较低，下丘脑TH染色像素密度和TH蛋白水平上调， 这种异常在P7和P30消失。 结论 孕期应激使子代下丘脑多巴胺神经元早期发育异常, 可能是造成子代神经系统行为学异常的原因之一。
Objective To investigate the effect of prenatal stress on the development of dopaminergic neurons in hypothalamus of rat offspring. Methods Restraint stress was performed three times each day for pregnant SD rats from embryonic day 12-19 in prenatal stress group. The day that the offspring was born was defined as the postnatal day 1. Dopamine expression in the hypothalamus of offspring was observed using the method of immunostaining on postnatal day 1, 7 and 30, respectively. Results Body weight of offspring rats in prenatal stress group significantly decreased, while the pixel intensity and level of dopamine in hypothalamus was up-regulated, compared with control group at the postnatal day 1(P<0.05). This change disappeared at the postnatal day 7 and 30. Conclusions Prenatal stress had an effect on the prenatal development of dopaminergic neurons in the hypothalamus, which may induce the long-term detrimental consequences for brain function.
Prenatal stress / Offspring / Hypothalamus / Dopaminergic neurons
[1] Huizink AC, Mulder EJ, Buitelaar JK. Prenatal stress and risk for psychology: specific effects or induction of general susceptibility
[J]? Psychol Bull, 2004,130 （1）:115-142.
[2] Verheij MM, Cools AR. Twenty years of dopamine research: individual differences in the response of accumbal dopamine to environmental and pharmacological challenges
[J]. Eur Jpharmacol,2008,585（2-3）:228-244.
[3] Barbaanges A，Piazza PV, Le Moal M,et al. Maternal glucocorticoid secretion mediates long-term effects of prenatal stress
[J]. J Neurosci,1996,16(12): 3343-3349.
[4] Lorey K, Takahashi A. Prenatal stress: consequences of glucocoids on hippocampal development and function
[J]. Int J Devl Neurosci,1998,16(3-4):199-207.
[5] Weinstock M. Alterations induced by gestational stress in brain morphology and behavior of the offspring
[J]. Prog Neurobiol, 2001,65(5):427-451.
[6] Nilsson PM, Nyberg P, Ostergren PO. Increased susceptibility to stress at a psychological assessment of stress tolerance is associated with impaired fetal growth
[J]. Int J Epidemiol,2001,30(1):75-80.
[7] Gale CR, Martyn CN. Birth weight and later risk of depression in a national birth cohort
[J]. Br J Psychiatry, 2004,184(1):28-33.
[8] Bock J, Murmu MS, Biala Y, et al. Prenatal stress and neonatal handling induce sex-specific changes in dendritic complexity and dendritic spine density in hippocampal subregions of prepubertal rats
[J]. Neuroscience, 2011,193(1):34-43.
[9] Koehl M, Darnaudery M, Dulluc J,et al. Prenatal stress alters circadian activity of hypothalamo-puitary-adrenal axis and hippocampal corticosteroid receptors in adult rats in both genders
[J]. J Neurobiol, 1999,40(3):302-315.
[10]Szuran TF, Pliska V, Pokorny J, et al. Prenatal stress in rats: effects on plasma corticosterone, hippocampal glucocorticoid receptors and maze performance
[J]. Physiol Behav, 2000,71(3-4）: 353-362.
[11]Weinstock M. Alterations induced by gestational stress in brain morphology and behavior of offspring
[J]. Prog Neurobiol,2001,65(5)?:427-451.
[12]Ward IL. Prenatal stress faminizes and demasculinizes the behavior of males
[J]. Science,1972,175(4017):82-84.
[13]Rhees RW, Al-Saleh HN, Kinghorn EW,et al. Relationship between sexual behavior and sexually dimorphic structures in the anterior hypothalamus in the control and prenatally stressed male rats
[J]. Brain Res Bull, 1999, 50(3):193-199.
[14]Baquedano E, García-Cáceres C, Diz-Chaves Y, et al. Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats
[J]. PLoS One,2011,6(11):e27549.
[15]Fujioka T, Sakata Y, Yamaguchi K, et al. The effects of prenatal stress on the development of hypothalamic paraventricular neurons in fetal rats
[J]. Neuroscience,1999,92（3）:1079-1088.
[16]McArthur S, McHale E, Gillies GE. The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner
[J]. Neuropsychopharmacology, 2007,32(7):1462-1476.
[17] Katunar MR, Saez T, Brusco A,et al. Immunocytochemical expression of dopamine-related transcription factors Pitx3 and Nurr1 in prenatally stressed adult rats
[J]. J Neurosci Res,2009,87(4):1014-1022.
广州市属高校科技、社科项目 (08A036)
京ICP备08002354号-3/
| 〈 |
|
〉 |
