Basha Riyaz, Reddy G Rajarami
M D Anderson Cancer Center, Orlando Cancer Research Institute, Orlando FL, USA.
Indian J Exp Biol. 2010 Jul;48(7):636-41.
Role of developmental exposure to environmental agents in altering the disease process is well known. Exposure to chemical agents at critical periods of development may cause some permanent changes in the functioning of various vital systems including the nervous system in the organisms. It is not surprising to see an extensive response due to exposure to chemical agents early in life as the organ systems are more vulnerable to chemical insults during developmental stages. In some cases the response to low level environmental insults may not be obvious until adult or old age. Results from several studies have shown such latency in response to the nervous system leading to neurodegeneration in old age. Studies conducted in murine and primate models provided ample evidence for the association of developmental exposure to low levels of heavy metal lead (Pb) and Alzheimer's disease-like pathology during senescence. It is not clear about the reasons behind such response; however, the contribution of epigenetic mechanisms could explain the role of early events in life in inducing the late life abnormalities of nervous system. It is possible that environmental agents epigenetically modulate the gene regulation to persist the response silent for a long period of time and to result pathological outcomes significantly later in life. This article will summarize the association of early life exposure to environmental agents and late-life abnormalities with an emphasis on developmental exposure to Pb and neurodegeneration in old age.
发育过程中接触环境因素对疾病进程的影响作用是众所周知的。在发育的关键时期接触化学物质可能会导致生物体各种重要系统(包括神经系统)的功能发生一些永久性变化。由于生命早期接触化学物质会引发广泛反应并不奇怪,因为在发育阶段器官系统更容易受到化学损伤。在某些情况下,对低水平环境损伤的反应可能直到成年或老年才会显现出来。多项研究结果表明,对神经系统的这种反应存在潜伏期,会导致老年时神经退行性变。在小鼠和灵长类动物模型中进行的研究为发育过程中接触低水平重金属铅(Pb)与衰老过程中阿尔茨海默病样病理之间的关联提供了充分证据。目前尚不清楚这种反应背后的原因;然而,表观遗传机制的作用可以解释生命早期事件在诱发神经系统晚年异常中的作用。环境因素有可能通过表观遗传调节基因表达,使反应长时间保持沉默,并在生命后期显著导致病理结果。本文将总结生命早期接触环境因素与晚年异常之间的关联,重点关注发育过程中接触铅与老年神经退行性变。