title: Mechanisms of late-onset cognitive decline after early-life stress.
abstract: 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.
authors.affiliation: Department of Anatomy/Neurobiology, University of California, Irvine, California 92697-4475, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Brunson
authors.forename: Enikö
authors.initials: E
authors.lastname: Kramár
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.forename: Yuncai
authors.initials: Y
authors.lastname: Chen
authors.forename: Laura Lee
authors.initials: LL
authors.lastname: Colgin
authors.forename: Theodore K
authors.initials: TK
authors.lastname: Yanagihara
authors.forename: Gary
authors.initials: G
authors.lastname: Lynch
authors.forename: Tallie Z
authors.initials: TZ
authors.lastname: Baram
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000818:Animals; D003072:Cognition Disorders / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008425:Maternal Behavior / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology*; D013997:Time Factors