EditorialStress in early life: Maternal protection and consequences
EditorialStress in early life: Maternal protection and consequences
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DOI：
10.1080/10253890500103764
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发表时间：
2005-03
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影响因子：
--
通讯作者：
J. Russell
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作者：
J. Russell
在最近出版的《压力》一书中，发表了几篇关于后代在出生前或出生后不久暴露在压力下对应激反应的持久后果或规划，以及随后关于晚年健康的评论(例如Gitau等人)。2001年，Maccari等人。2001年，Schneider等人。2001年，Ward和Phillips，2001，Pedersen&Boccia，2002，Weinstock，2002，Andrews&Matthews 2004)。这一领域的重要性是显而易见的，无论是在个人方面还是在社会经济和福利后果方面。这一以压力为主题的问题扩展了这一系列权威的、最新的关于该领域最新研究和争议的描述，特别是对人类的研究。然而，从对动物的研究中可以清楚地看出，这两种类型的调查--关于人类的调查和关于动物模型的调查--是相辅相成的，动物研究能够以一种人类研究不可能的方式深入探索机制。此外，重要的是要了解动物模型在人类应激反应编程问题上的局限性，以便更好地制定研究问题，然后有望改善对怀孕和母婴相互作用的不良影响的管理。Douglas(2005)回顾了与她的同事一起对怀孕大鼠的母体下丘脑-垂体-肾上腺(HPA)轴对一系列应激源反应减少的现象的研究结果。这些研究集中在脑干去甲肾上腺素能神经元投射到室旁核促肾上腺皮质激素释放因子(CRF)神经元的变化，该神经元由循环中的CCK(可引起恶心)的急剧增加激活，但也参与处理其他情绪应激源的中央网络。这些研究表明，在任何一种刺激下，ACTH分泌反应的减少可能部分是由于抑制了去甲肾上腺素释放到CRF神经元上的结果，正如先前在哺乳中所显示的那样。妊娠期室旁核A1a-肾上腺素能受体mRNA表达的降低也表明去甲肾上腺素输入的活性降低。这可能是去甲肾上腺素的抑制释放反映了内源性阿片机制的抑制，以前已经证明这是导致妊娠期间HPA轴反应减少的原因(Douglas&Russell 2001)。从这些研究中还不清楚怀孕是如何向大脑发出信号来诱导阿片类药物机制的激活，或者以其他方式减少HPA轴的反应。这种信号似乎不是性激素作用的结果，也不是催产素对CRF神经元局部作用的结果。对于道格拉斯研究的应激源，HPA轴反应在怀孕期间的衰减还不完全，在去甲肾上腺素输入无效的情况下，哪些通往CRF神经元的途径在怀孕期间仍然有效，仍有待澄清。正如屠维平等人所讨论的那样，当母亲将应激源解释为对后代特别威胁时，这些途径可能被用来克服哺乳期HPA反应性的降低。(2005)。屠呦呦等人。(2005)解决了妇女在怀孕和哺乳期间对压力的反应改变的问题，利用对啮齿动物的研究来提供对机制的见解。他们简要回顾了对啮齿动物的研究，这些研究表明HPA轴的应激反应在怀孕期间会减弱，Douglas(2005)更详细地讨论了这一点，并将这些发现与女性缺乏这一问题的数据进行了对比。关于孕妇对压力源的反应的研究很难规划，原因很明显，可用于基于实验室的孕妇研究的压力源类型同样有限；此外，胎盘的干预使问题复杂化，胎盘会在妇女中产生CRF。就像在怀孕期间一样，对啮齿动物的研究表明，在哺乳期，HPA轴对一系列应激源的反应显著减弱，其机制最终涉及驱动ACTH的下丘脑CRF神经元的激活，从而减少皮质酮的分泌。大脑中的应激源处理电路也会发生变化
Several reviews have been published in recent volumes of Stress on the enduring consequences, or programming, following exposure of offspring to stress before or soon after birth on stress reactivity, and consequently on health in later life (e.g. Gitau et al. 2001, Maccari et al. 2001, Schneider et al. 2001, Ward and Phillips, 2001, Pedersen & Boccia 2002, Weinstock, 2002, Andrews & Matthews 2004). The importance of this area is obvious, both in relation to individuals and the socio-economic and welfare consequences. This themed issue of Stress extends this series of authoritative, up-to-date accounts of recent research and controversies in the field, with a particular focus on studies on humans. Nonetheless it should be clear from the accounts of studies on animals that are included here that these two types of investigation, on humans and on animal models, are complementary, with animal studies able to deeply probe mechanisms in a way that is not possible in human studies. Moreover, it is important that the limitations of animal models in their applicability to the questions about programming of human stress responses are understood, in order to progress to better formulation of research questions, and hopefully then to improve the management of malign influences on pregnancy and mother–infant interactions. Douglas (2005) reviews findings from studies with her colleagues on the phenomenon of reduced responses of the maternal hypothalamo–pituitary– adrenal (HPA) axis to a range of stressors in pregnant rats. These studies have focused on changes in the brainstem noradrenergic neurone projection to the corticotrophin releasing factor (CRF) neurones in the paraventricular nucleus, which is activated by an acute increase in circulating cholecystokinin (that can induce nausea), but is also involved in the central network processing other, emotional stressors. These studies show that the reduced ACTH secretory response that follows either type of stimulus is likely to be in part a result of suppressed noradrenaline release onto the CRF neurones, as previously shown in lactation. A decrease in pregnancy in a1A-adrenergic receptor mRNA expression in the paraventricular nucleus also indicates reduced activity of the noradrenegic input. It may be that the suppressed release of noradrenaline reflects inhibition by the endogenous opioid mechanisms that have been previously shown to contribute to reduced HPA axis responses in pregnancy (Douglas & Russell 2001). It is not yet clear from these studies how pregnancy signals to the brain to induce activation of this opioid mechanism, or to otherwise reduce HPA axis responses. This signalling does not seem to be a result of sex steroid action, nor a consequence of local action of oxytocin on CRF neurones. For the stressors that Douglas has investigated the attenuation of HPA axis responses in pregnancy is not complete, and it remains to be clarified which pathways to CRF neurones, given ineffectiveness of the noradrenergic input, remain operational in pregnancy. It may be that these pathways are used to overcome reduced HPA responsiveness in lactation when the stressor is interpreted by the mother as particularly threatening to the offspring, as discussed by Tu et al. (2005). Tu et al. (2005) address the issue of the altered responsiveness to stress in pregnancy and in lactation in women, drawing on the studies in rodents to provide insights into mechanisms. They briefly review the studies on rodents, which show that stress responses of the HPA axis are attenuated in pregnancy, as discussed in more detail by Douglas (2005), and contrast these findings with the lack of data on this question in women. There are obvious reasons why studies on responses of pregnant women to stressors are difficult to plan, and the types of stressor that can be used in laboratorybased studies on pregnant women are similarly limited; furthermore, the intervention of the placenta, which produces CRF in women, complicates the issue. As in pregnancy, studies on rodents have shown a remarkable attenuation of HPA axis responses to a range of stressors in lactation, and mechanisms for this involve finally a reduced activation of the hypothalamic CRF neurones that drive ACTH and hence corticosterone secretion. There are also changes in the stressor processing circuits in the brain