Mechanisms of late-onset cognitive decline after early-life stress
Mechanisms of late-onset cognitive decline after early-life stress
复制标题
DOI：
10.1523/jneurosci.2281-05.2005
复制
发表时间：
2005-10-12
影响因子：
5.3
通讯作者：
Baram, TZ
中科院分区：
文献类型：
--
作者：
Brunson, KL;Kramár, E;Baram, TZ
随着年龄的增长而出现的渐进性认知缺陷是遗传和环境因素复杂相互作用的结果。尽管人们对这些疾病的遗传基础已经了解了很多，但“获得性”因素的性质以及它们促进渐进性学习和记忆功能障碍的机制在很大程度上仍然未知。在这里，我们证明了一段时间的早期生活的“心理”压力导致迟发性，选择性恶化的复杂行为和突触可塑性：两种形式的记忆涉及海马，严重，但选择性受损的中年，但不是年轻的成年人，大鼠暴露于支离破碎的孕产妇护理在出生后早期。在细胞水平上，海马长时程增强的紊乱会导致行为学改变，并伴有树突萎缩和苔藓纤维扩张。这些发现构成了第一个证据，表明生命早期的短期压力可能导致海马功能的突触和行为措施的延迟，进行性损伤，对人类年龄相关认知障碍的基础具有潜在影响。
Progressive cognitive deficits that emerge with aging are a result of complex interactions of genetic and environmental factors. Whereas much has been learned about the genetic underpinnings of these disorders, the nature of "acquired" contributing factors, and the mechanisms by which they promote progressive learning and memory dysfunction, remain largely unknown. Here, we demonstrate that a period of early-life "psychological" stress causes late-onset, selective deterioration of both complex behavior and synaptic plasticity: two forms of memory involving the hippocampus, were severely but selectively impaired in middle-aged, but not young adult, rats exposed to fragmented maternal care during the early postnatal period. At the cellular level, disturbances to hippocampal long-term potentiation paralleled the behavioral changes and were accompanied by dendritic atrophy and mossy fiber expansion. These findings constitute the first evidence that a short period of stress early in life can lead to delayed, progressive impairments of synaptic and behavioral measures of hippocampal function, with potential implications to the basis of age-related cognitive disorders in humans.