Brunson Kristen L, Kramár Enikö, Lin Bin, Chen Yuncai, Colgin Laura Lee, Yanagihara Theodore K, Lynch Gary, Baram Tallie Z
Department of Anatomy/Neurobiology, University of California, Irvine, California 92697-4475, USA.
J Neurosci. 2005 Oct 12;25(41):9328-38. doi: 10.1523/JNEUROSCI.2281-05.2005.
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.
随着年龄增长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。尽管人们已经对这些疾病的遗传基础有了很多了解，但“后天获得的”促成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，我们证明早期生活中的一段“心理”应激会导致迟发性、选择性的复杂行为和突触可塑性衰退：两种涉及海马体的记忆形式，在出生后早期经历碎片化母性照料的中年大鼠中严重但选择性地受损，而在年轻成年大鼠中未受损。在细胞水平上，海马体长期增强的紊乱与行为变化平行，并伴有树突萎缩和苔藓纤维扩张。这些发现首次证明，生命早期的短期应激会导致海马体功能的突触和行为指标出现延迟的、渐进性的损害，这可能对人类与年龄相关的认知障碍的基础产生影响。
