Department of Physiology, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia.
Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E11-8. doi: 10.1152/ajpendo.00516.2010. Epub 2010 Nov 2.
The early life environment can be crucial in influencing the development of an animal's long-term physiology. There is now much evidence to suggest that perinatal challenges to an animal's immune system will result in changes in adult rat behavior, physiology, and molecular pathways following a single inflammatory event during development caused by the bacterial endotoxin lipopolysaccharide (LPS). In particular, it is now apparent that neonatal LPS administration can influence the adult neuroimmune response to a second LPS challenge through hypothalamic-pituitary-adrenal axis modifications, some of which are caused by alterations in peripheral prostaglandin synthesis. These pronounced changes are accompanied by a variety of alterations in a number of disparate aspects of endocrine physiology, with significant implications for the health and well-being of the adult animal. In this review, we discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal's endocrine and metabolic physiology and the implications this has for various disease states.
早期生活环境在影响动物的长期生理发育方面起着至关重要的作用。现在有很多证据表明,动物免疫系统在围产期受到挑战,会导致成年大鼠在发育过程中单次炎症事件(由细菌内毒素脂多糖(LPS)引起)后,其行为、生理和分子途径发生变化。特别是,现在很明显,新生儿 LPS 给药可以通过下丘脑-垂体-肾上腺轴的改变来影响成年后对第二次 LPS 挑战的神经免疫反应,其中一些改变是由外周前列腺素合成的改变引起的。这些明显的变化伴随着内分泌生理学许多不同方面的各种改变,这对成年动物的健康和幸福有重大影响。在这篇综述中,我们讨论了新生儿免疫挑战可以永久性改变动物的内分泌和代谢生理学的新阐明的机制,以及这对各种疾病状态的影响。