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

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.

Acute stress and working memory in older people

“…In contrast to the clear effects observed in young adults (for a review see Wolf, 2009), previous studies in older animals and humans did not show any acute effects on spatial memory (Buechel et al, 2014), learning, short-term declarative or non-declarative memory (Porter et al, 2002), or long-term memory retrieval of pictures, words and stories (Pulopulos et al, 2013). However, we have observed a specific effect of stress-induced cortisol response on retroactive interference (i.e.…”

Constitutive differences in glucocorticoid responsiveness are related to divergent spatial information processing abilities

“…Similarly, these glucocorticoid regulation characteristics might help as well explaining why the High CORT line did not show deleterious performance in the spatial task despite the fact that they were tested during early aging. This is particularly relevant given the substantial evidence in rodents and humans implicating midlife stress (Borcel et al, 2008; Sandi and Touyarot, 2006) and cumulative exposure to high glucocorticoid levels in age-related cognitive impairments (Bodnoff et al, 1995; Buechel et al, 2014; Landfield et al, 1981; Lupien et al, 1998; Lupien and McEwen, 1997; Wheelan et al, 2018; Yau et al, 2015). It was also shown, in various species, that aged individuals are impaired in spatial reversal learning (Eppinger et al, 2011; Lai et al, 1995; Mongillo et al, 2013).…”

Evidence for an apathy phenotype in aged mice

“…However, it has been previously suggested that changes to the functional gating of limbic information by local PVN projections may explain age-related changes to the HPA axis (Herman et al, 2002). Stress reactivity and active coping in response to aversive experiences has previously been shown to reduce with age in mice (Oh et al, 2018) and extend beyond mice to rat and human studies (Brugnera et al, 2017;Buechel et al, 2014). There is some variability in findings possibly due to a lack of standardisation across studies including the nature and intensity of the stressor (Novais et al, 2017;Segar et al, 2009).…”