Behavioral, Hormonal, and Tissue Biomarkers of Stress Regulation in Young Adult Rats after Different Schedules of Early Life Stress: Eustress versus Distress
Date
2014-09-18
Authors
Stoneham, Emily T.
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Abstract
Individuals experiencing stressful early life environments due to isolation, abuse, or neglect, are predisposed not only toward physically debilitating illnesses (coronary and metabolic diseases) but also potentially devastating neuropsychiatric disorders (post- traumatic stress disorder, memory impairment, depression). Memory loss in adults exposed to early life stress is primarily the result of an altered cortisol homeostasis and most often involves hippocampal dysfunction. Interestingly, timing of early life stress with respect to developmental stage and predictability of stressful episodes is critical in determining the magnitude of future adult disorders. Conventional early life stress studies in rats use one of two maternal separation paradigms. In the daily stress model, separation occurs every day, typically during the first postnatal week. For the intermittent stress model, separation occurs more randomly. Because different separation schedules have been employed independently, varying reports could result from any number of undocumented variables. Moreover, prior work has focused on outcome in middle aged and older rats, preventing discovery of early biomarkers for impending memory loss. As such, we applied daily or intermittent maternal separation and, in young adulthood, we examined behavioral and hormonal variables indicative of hippocampal integrity. We discovered that daily maternal separation impaired spatial learning, while intermittent maternal separation tended to improve spatial memory in young adults. This research also showed that daily and intermittent separation paradigms produce opposing hormonal profiles that may serve as biomarkers predictive of impending memory dysfunction at older ages. Interestingly, elevation in stress hormone levels became dependent on brain- derived neurotrophic factor following intermittent separation. Attempts to recuperate recover normal spatial cognition by overexpressing glucocorticoid and estrogen related proteins in the hippocampus proved ineffective.
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Stress regulation