Limits...
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

Panel of aging genes. (A) Venn diagram. Of 171 established aging genes, 115 are changed significantly in this study (two way ANOVA; significant main effects of aging or stress, or interaction p ≤ 0.05). (B) Direction of Change. Nearly complete agreement with prior studies regarding direction of change for aging-sensitive genes. (C) Genes down-regulated in previous studies. (D) Genes up-regulated in previous studies. Color: Blue, down; Red, Up, Shading; Dark, age significant; light, age non-significant; Bold, stress-significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921565&req=5

Figure 6: Panel of aging genes. (A) Venn diagram. Of 171 established aging genes, 115 are changed significantly in this study (two way ANOVA; significant main effects of aging or stress, or interaction p ≤ 0.05). (B) Direction of Change. Nearly complete agreement with prior studies regarding direction of change for aging-sensitive genes. (C) Genes down-regulated in previous studies. (D) Genes up-regulated in previous studies. Color: Blue, down; Red, Up, Shading; Dark, age significant; light, age non-significant; Bold, stress-significant.

Mentions: Hippocampal mRNA was tested for aging and stress changes against an “aging” panel of 171 genes found to change significantly with age in at least two of three published hippocampal aging microarray studies in male F344 rats (see Methods). As predicted, far more genes are significant than could be reasonably explained by multiple testing error (115 found vs. 9 expected with 171 tests at α = 0.05) and are primarily centered on aging (Figure 6A). Additionally, nearly all significant genes in the present study also agreed in direction of change with prior work on aging (Figure 6B). Even non-significant genes showed >80% agreement in direction of change with prior aging studies (p < 0.001, binomial test). Genes altered with age were largely associated with results as reported in prior work, including down-regulated neuronal and synaptic markers, and up-regulated immune and inflammatory signaling. All 171 genes in the aging panel are shown in Figure 6C (for genes previously defined as up-regulated with age) and 6D (for genes previously defined as down-regulated), and color-coded with their results in the present study (complete descriptions are available in Supplemental Table 1).


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)

Panel of aging genes. (A) Venn diagram. Of 171 established aging genes, 115 are changed significantly in this study (two way ANOVA; significant main effects of aging or stress, or interaction p ≤ 0.05). (B) Direction of Change. Nearly complete agreement with prior studies regarding direction of change for aging-sensitive genes. (C) Genes down-regulated in previous studies. (D) Genes up-regulated in previous studies. Color: Blue, down; Red, Up, Shading; Dark, age significant; light, age non-significant; Bold, stress-significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Panel of aging genes. (A) Venn diagram. Of 171 established aging genes, 115 are changed significantly in this study (two way ANOVA; significant main effects of aging or stress, or interaction p ≤ 0.05). (B) Direction of Change. Nearly complete agreement with prior studies regarding direction of change for aging-sensitive genes. (C) Genes down-regulated in previous studies. (D) Genes up-regulated in previous studies. Color: Blue, down; Red, Up, Shading; Dark, age significant; light, age non-significant; Bold, stress-significant.
Mentions: Hippocampal mRNA was tested for aging and stress changes against an “aging” panel of 171 genes found to change significantly with age in at least two of three published hippocampal aging microarray studies in male F344 rats (see Methods). As predicted, far more genes are significant than could be reasonably explained by multiple testing error (115 found vs. 9 expected with 171 tests at α = 0.05) and are primarily centered on aging (Figure 6A). Additionally, nearly all significant genes in the present study also agreed in direction of change with prior work on aging (Figure 6B). Even non-significant genes showed >80% agreement in direction of change with prior aging studies (p < 0.001, binomial test). Genes altered with age were largely associated with results as reported in prior work, including down-regulated neuronal and synaptic markers, and up-regulated immune and inflammatory signaling. All 171 genes in the aging panel are shown in Figure 6C (for genes previously defined as up-regulated with age) and 6D (for genes previously defined as down-regulated), and color-coded with their results in the present study (complete descriptions are available in Supplemental Table 1).

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