Article

Hippocampal damage associated with prolonged and fatal stress primates

Regional Primate Research Center, University of Wisconsin, Madison 53715-1299.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 06/1989; 9(5):1705-11.
Source: PubMed

ABSTRACT

Sustained exposure to glucocorticoids (GCs), adrenal hormones secreted during stress, can cause neural degeneration in the rat. This is particularly so in the hippocampus, a principal neural target site for GCs, in which GCs can exacerbate the rate of neuron death during normal aging, as well as the severity of neuronal damage after various neurological insults. Thus, stress can be a potent modulator of hippocampal degeneration in the rat. The present report suggests a similar association in the primate. Eight vervet monkeys, housed in a primate center in Kenya, that had died spontaneously from 1984 to 1986, were found at necropsy to have multiple gastric ulcers; a retrospective, neuropathological study was then done of this opportunistic population. Compared with controls euthanized for other research purposes, ulcerated monkeys had marked hippocampal degeneration that was apparent both quantitatively and qualitatively, and both ultrastructurally and on the light-microscopic level. Minimal damage occurred outside the hippocampus. Damage was unlikely to have been due to an agonal or post-mortem artifact. Instead, ulcerated monkeys appear to have been subject to sustained social stress, perhaps in the form of social subordinance in captive breeding groups: most came from social groups, had significantly high incidences of bite wounds at necropsy, and had hyperplastic adrenal cortices, indicative of sustained GC release. Moreover, the specific hippocampal cell fields damaged in ulcerated animals matched those damaged by GCs in the rodent hippocampus. Thus, this represents the first evidence suggesting that sustained stress, via GC hypersecretion, might be neurodegenerative in the primate.

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    • "A brain region most sensitive to stress-and glucocorticoid-induced morphological changes is the hippocampus, which contains high levels of the mineral-and glucocorticoid receptors (MR and GR, respectively) (Reul and de Kloet, 1985). Within the hippocampal formation, the CA3 pyramidal cells of both rodents and primates are particularly vulnerable to dendritic remodeling, neuronal damage, and cell loss associated with excess CRH, prolonged social stress and glucocorticoid treatment (Chen et al., 2010;Ribak and Baram, 1996;Sapolsky et al., 1985;Uno et al., 1989Uno et al., , 1990). In addition, more recently, evidence has been provided that GRs are present in hippocampal dendritic spines where they mediate acute, non-genomic glucocorticoid effects on local spine signaling (Jafari et al., 2012). "

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    • "When these situations occur infrequently, this is a valid coping strategy. However, if an individual is constantly exposed to a dangerous situation, this can manifest in allostatic load, where the constant activation of the autonomic and adrenocortical systems required for homeostasis causes damage over time (McEwen, 2000;Selye, 1936), including hypertension (Melin et al., 1999) and potential neuronal atrophy (Sapolsky, 1996;Uno et al., 1989). Attempts to mitigate allostatic load focus on social and cognitive therapies (see Section 8), but also investigate those individuals who have natural resilience to stress (''achieving a positive outcome in the face of adversity " ;McEwen et al., 2015), and it may be that certain individuals are more suited for work in stressful environments than others. "
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    • "Depleted area of MF terminals, dendritic atrophy, nuclear pyknosis in the CA3, soma shrinkage and cell loss in the CA1, CA3 subfields. Reduced hippocampal proliferation and survival Enhanced LTP threshold and potentiated LTD in the CA1 Impaired memory in the NOR task and the Y maze test Uno et al., 1989; Magarinos et al., 1996; McKittrick et al., 2000; Czeh et al., 2001; Rygula et al., 2005; Lagace et al., 2010; Wang et al., 2011a; Wagner et al., 2013 Uncontrollable stress (inescapable shock) Reduced hippocampal proliferation Impaired LTP, enhanced LTD in the CA1 Impaired object recognition memory in long acquisition to retrieval delay test Shors et al., 1989; de Quervain et al., 1998; Dagyte et al., 2009 Mixed stress "
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