RT Journal Article SR Electronic T1 Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9328 OP 9338 DO 10.1523/JNEUROSCI.2281-05.2005 VO 25 IS 41 A1 Brunson, Kristen L. A1 Kramár, Enikö A1 Lin, Bin A1 Chen, Yuncai A1 Colgin, Laura Lee A1 Yanagihara, Theodore K. A1 Lynch, Gary A1 Baram, Tallie Z. YR 2005 UL http://www.jneurosci.org/content/25/41/9328.abstract AB 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.