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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

Electrophysiology. (A) EPSP slope plotted as a function of stimulus voltage for each age and restraint condition. For statistical testing, stimulus voltage was categorized (i.e., voltage steps 1–10). By two way repeated measures ANOVA, stimulus significantly influenced slope (p < 0.001), while there was no significant group effect. However, interaction was significant (p < 0.05). Post hoc pairwise results (Fisher's LSD; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001) contrast young control and aged control and reveal significant deflection of aged control EPSP slope especially at steps 7–10. (B) Paired pulse facilitation plotted as a function of delay for each age and restraint condition. There was a significant effect of delay (p < 0.001) but not group or interaction (two way repeated measures ANOVA).
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Figure 4: Electrophysiology. (A) EPSP slope plotted as a function of stimulus voltage for each age and restraint condition. For statistical testing, stimulus voltage was categorized (i.e., voltage steps 1–10). By two way repeated measures ANOVA, stimulus significantly influenced slope (p < 0.001), while there was no significant group effect. However, interaction was significant (p < 0.05). Post hoc pairwise results (Fisher's LSD; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001) contrast young control and aged control and reveal significant deflection of aged control EPSP slope especially at steps 7–10. (B) Paired pulse facilitation plotted as a function of delay for each age and restraint condition. There was a significant effect of delay (p < 0.001) but not group or interaction (two way repeated measures ANOVA).

Mentions: Animals were killed the day following restraint and hippocampal slices were prepared for extracellular synaptic recordings. Input/output (I/O) experiments assessed the relationship between synaptic response (output) and stimulus (input) (Figure 4A). Aged control animals showed a significantly weakened input/output relationship, as has been seen in prior studies (Barnes and McNaughton, 1980; Landfield et al., 1986). This weakening appeared, at least in part, recovered in stressed aged subjects. We also tested for presynaptic calcium perturbations using the PP facilitation (Figure 4B) protocol. As in previous studies (Landfield et al., 1978a; Wu and Saggau, 1994), no age-related changes were detected. Further, no change was seen in either of these measures with stress exposure.


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)

Electrophysiology. (A) EPSP slope plotted as a function of stimulus voltage for each age and restraint condition. For statistical testing, stimulus voltage was categorized (i.e., voltage steps 1–10). By two way repeated measures ANOVA, stimulus significantly influenced slope (p < 0.001), while there was no significant group effect. However, interaction was significant (p < 0.05). Post hoc pairwise results (Fisher's LSD; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001) contrast young control and aged control and reveal significant deflection of aged control EPSP slope especially at steps 7–10. (B) Paired pulse facilitation plotted as a function of delay for each age and restraint condition. There was a significant effect of delay (p < 0.001) but not group or interaction (two way repeated measures ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Electrophysiology. (A) EPSP slope plotted as a function of stimulus voltage for each age and restraint condition. For statistical testing, stimulus voltage was categorized (i.e., voltage steps 1–10). By two way repeated measures ANOVA, stimulus significantly influenced slope (p < 0.001), while there was no significant group effect. However, interaction was significant (p < 0.05). Post hoc pairwise results (Fisher's LSD; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001) contrast young control and aged control and reveal significant deflection of aged control EPSP slope especially at steps 7–10. (B) Paired pulse facilitation plotted as a function of delay for each age and restraint condition. There was a significant effect of delay (p < 0.001) but not group or interaction (two way repeated measures ANOVA).
Mentions: Animals were killed the day following restraint and hippocampal slices were prepared for extracellular synaptic recordings. Input/output (I/O) experiments assessed the relationship between synaptic response (output) and stimulus (input) (Figure 4A). Aged control animals showed a significantly weakened input/output relationship, as has been seen in prior studies (Barnes and McNaughton, 1980; Landfield et al., 1986). This weakening appeared, at least in part, recovered in stressed aged subjects. We also tested for presynaptic calcium perturbations using the PP facilitation (Figure 4B) protocol. As in previous studies (Landfield et al., 1978a; Wu and Saggau, 1994), no age-related changes were detected. Further, no change was seen in either of these measures with stress exposure.

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