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Featured ArticleArticles, Systems/Circuits

Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory

Rachel M. Anderson, Andrew K. Birnie, Norah K. Koblesky, Sara A. Romig-Martin and Jason J. Radley
Journal of Neuroscience 18 June 2014, 34 (25) 8387-8397; DOI: https://doi.org/10.1523/JNEUROSCI.1385-14.2014
Rachel M. Anderson
Psychology Department and Neuroscience Program, University of Iowa, Iowa City, Iowa 52242
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Andrew K. Birnie
Psychology Department and Neuroscience Program, University of Iowa, Iowa City, Iowa 52242
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Norah K. Koblesky
Psychology Department and Neuroscience Program, University of Iowa, Iowa City, Iowa 52242
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Sara A. Romig-Martin
Psychology Department and Neuroscience Program, University of Iowa, Iowa City, Iowa 52242
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Jason J. Radley
Psychology Department and Neuroscience Program, University of Iowa, Iowa City, Iowa 52242
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Abstract

Cognitive decline in aging is marked by considerable variability, with some individuals experiencing significant impairments and others retaining intact functioning. Whereas previous studies have linked elevated hypothalamo-pituitary-adrenal (HPA) axis activity with impaired hippocampal function during aging, the idea has languished regarding whether such differences may underlie the deterioration of other cognitive functions. Here we investigate whether endogenous differences in HPA activity are predictive of age-related impairments in prefrontal structural and behavioral plasticity. Young and aged rats (4 and 21 months, respectively) were partitioned into low or high HPA activity, based upon averaged values of corticosterone release from each animal obtained from repeated sampling across a 24 h period. Pyramidal neurons in the prelimbic area of medial prefrontal cortex were selected for intracellular dye filling, followed by 3D imaging and analysis of dendritic spine morphometry. Aged animals displayed dendritic spine loss and altered geometric characteristics; however, these decrements were largely accounted for by the subgroup bearing elevated corticosterone. Moreover, high adrenocortical activity in aging was associated with downward shifts in frequency distributions for spine head diameter and length, whereas aged animals with low corticosterone showed an upward shift in these indices. Follow-up behavioral experiments revealed that age-related spatial working memory deficits were exacerbated by increased HPA activity. By contrast, variations in HPA activity in young animals failed to impact structural or behavioral plasticity. These data implicate the cumulative exposure to glucocorticoids as a central underlying process in age-related prefrontal impairment and define synaptic features accounting for different trajectories in age-related cognitive function.

  • corticosterone
  • HPA axis
  • medial prefrontal cortex
  • prelimbic
  • working memory
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The Journal of Neuroscience: 34 (25)
Journal of Neuroscience
Vol. 34, Issue 25
18 Jun 2014
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Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory
Rachel M. Anderson, Andrew K. Birnie, Norah K. Koblesky, Sara A. Romig-Martin, Jason J. Radley
Journal of Neuroscience 18 June 2014, 34 (25) 8387-8397; DOI: 10.1523/JNEUROSCI.1385-14.2014

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Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory
Rachel M. Anderson, Andrew K. Birnie, Norah K. Koblesky, Sara A. Romig-Martin, Jason J. Radley
Journal of Neuroscience 18 June 2014, 34 (25) 8387-8397; DOI: 10.1523/JNEUROSCI.1385-14.2014
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Keywords

  • corticosterone
  • HPA axis
  • medial prefrontal cortex
  • prelimbic
  • working memory

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