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Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging.

Buechel HM, Popovic J, Staggs K, Anderson KL, Thibault O, Blalock EM - Front Aging Neurosci (2014)

Bottom Line: In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events.We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes.These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

View Article: PubMed Central - PubMed

Affiliation: Blalock Laboratory, Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky Lexington, KY, USA.

ABSTRACT
Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 month) and aged (21 month) male F344 rats into control and acute restraint (an animal model of psychosocial stress) groups (n = 9-12/group). We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the 3 h restraint, as well as highly significant increases in blood glucocorticoid levels 21 h after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

No MeSH data available.


Related in: MedlinePlus

Stress influence on control-only aging-significant genes. (A) Table of control-only significant genes separated by directional influence of stress within young and within aged subjects. (A-inset): Venn diagram of pairwise contrast results- a majority of aging-significant genes were significant in both control and stressed groups. However relatively few genes were selectively changed with age in the stress condition. Instead, control-only aging significant genes appeared relatively enriched. (B) Stress' influence on age-related gene expression. Individual gene expression stress effect sizes [(stress mean–control mean)/pooled SD] within young (x axis) or within aged (y axis) subjects is plotted.
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Figure 7: Stress influence on control-only aging-significant genes. (A) Table of control-only significant genes separated by directional influence of stress within young and within aged subjects. (A-inset): Venn diagram of pairwise contrast results- a majority of aging-significant genes were significant in both control and stressed groups. However relatively few genes were selectively changed with age in the stress condition. Instead, control-only aging significant genes appeared relatively enriched. (B) Stress' influence on age-related gene expression. Individual gene expression stress effect sizes [(stress mean–control mean)/pooled SD] within young (x axis) or within aged (y axis) subjects is plotted.

Mentions: To better depict stress' influence on the aging transcriptional profile, we performed pairwise contrast analyses (Figure 7A- Inset Venn). A large cohort of genes (43) significantly changed with age regardless of stress status, but relatively few genes (8) changed with age in the stress-only condition. In contrast, a large group of genes (42) changed with age in control, but not stressed, subjects (listed in 7A). Taken together, these data suggest that young and aged subjects' transcriptional profiles become more similar to one another under stress conditions.


Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging.

Buechel HM, Popovic J, Staggs K, Anderson KL, Thibault O, Blalock EM - Front Aging Neurosci (2014)

Stress influence on control-only aging-significant genes. (A) Table of control-only significant genes separated by directional influence of stress within young and within aged subjects. (A-inset): Venn diagram of pairwise contrast results- a majority of aging-significant genes were significant in both control and stressed groups. However relatively few genes were selectively changed with age in the stress condition. Instead, control-only aging significant genes appeared relatively enriched. (B) Stress' influence on age-related gene expression. Individual gene expression stress effect sizes [(stress mean–control mean)/pooled SD] within young (x axis) or within aged (y axis) subjects is plotted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921565&req=5

Figure 7: Stress influence on control-only aging-significant genes. (A) Table of control-only significant genes separated by directional influence of stress within young and within aged subjects. (A-inset): Venn diagram of pairwise contrast results- a majority of aging-significant genes were significant in both control and stressed groups. However relatively few genes were selectively changed with age in the stress condition. Instead, control-only aging significant genes appeared relatively enriched. (B) Stress' influence on age-related gene expression. Individual gene expression stress effect sizes [(stress mean–control mean)/pooled SD] within young (x axis) or within aged (y axis) subjects is plotted.
Mentions: To better depict stress' influence on the aging transcriptional profile, we performed pairwise contrast analyses (Figure 7A- Inset Venn). A large cohort of genes (43) significantly changed with age regardless of stress status, but relatively few genes (8) changed with age in the stress-only condition. In contrast, a large group of genes (42) changed with age in control, but not stressed, subjects (listed in 7A). Taken together, these data suggest that young and aged subjects' transcriptional profiles become more similar to one another under stress conditions.

Bottom Line: In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events.We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes.These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

View Article: PubMed Central - PubMed

Affiliation: Blalock Laboratory, Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky Lexington, KY, USA.

ABSTRACT
Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 month) and aged (21 month) male F344 rats into control and acute restraint (an animal model of psychosocial stress) groups (n = 9-12/group). We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the 3 h restraint, as well as highly significant increases in blood glucocorticoid levels 21 h after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

No MeSH data available.


Related in: MedlinePlus