Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators

In the paper

“Although glucocorticoids and catecholamines are the two defining hormones of the “fight or flight” stress response, there are many other mediators, such as pro- and anti-inflammatory cytokines and the parasympathetic nervous system, that are also involved in the adaptation to stressors, as well as in the negative impact of chronic stress, known in every day language as being “stressed out”.”

In the paper

“The brain is the central organ of the stress response and determines what is stressful, as well as the behavioral and physiological responses to potential and actual stressors.”

In the paper

“The adaptive plasticity of chronic stress involves many mediators, including glucocorticoids, excitatory amino acids, endogenous factors such as brain neurotrophic factor (BDNF), polysialated neural cell adhesion molecule (PSA-NCAM) and tissue plasminogen activator (tPA).”

In the paper

“The brain is also a target of stress and it changes structurally and chemically in response to both acute and chronic stressors.”

In the paper

“Chronic stress can promote and exacerbate pathophysiology through the same systems that are dysregulated.”

In the paper

“Acute stress responses promote adaptation and survival via responses of neural, cardiovascular, autonomic, immune and metabolic systems.”

In the paper

“Indeed, there are important differences in the effects of acute and chronic stress, as well as differences in the consequences of acute and chronic treatment with glucocorticoids.”

In the paper

“Glucocorticoids play a role in these changes, but there are other mediators as well.”

In the paper

“on the one hand, the body responds to almost any sudden, unexpected event by releasing chemical mediators – e.g. catecholamines that increase heart rate and blood pressure – and help the individual cope with the situation”

What the sources say

• Not checked yetcites McEwen, 1998 source

In the paper

“Brain regions such as hippocampus, prefrontal cortex and amygdala respond to acute and chronic stress and show changes in morphology and chemistry that are largely reversible if the chronic stress lasts for weeks.”

In the paper

“Stress begins in the brain and affects the brain, as well as the rest of the body.”

In the paper

“For example, the short form of the serotonin transporter is associated with a number of conditions such as alcoholism, and individuals who have this allele are more vulnerable to respond to stressful experiences by developing depressive illness (Caspi et al., 2003).”

What the sources say

• Not checked yetcites Caspi et al., 2003 source

In the paper

“There are enormous individual differences in the response to stress, based upon the experience of the individual early in life and in adult life.”

In the paper

“For example, uncertainty in the food supply for rhesus monkey mothers leads to increased emotionality in offspring and possibly an earlier onset of obesity and diabetes (Coplan et al., 2001).”

What the sources say

• Not checked yetcites Coplan et al., 2001 source

In the paper

“Regarding allostasis, in Spring, a sudden snowstorm is an acute stressor to birds and disrupts mating, and elevated cortisol is pivotal in directing the birds to suspend reproduction, to find a source of food and to relocate to a better mating site or at least to delay reproduction until the weather improves (Wingfield and Romero, 2000).”

What the sources say

• Not checked yetcites Wingfield and Romero, 2000

In the paper

“Furthermore, in rodents, abuse of the young is associated with an attachment, rather than an avoidance, of the abusive mother, an effect that increases the chances that the infant can continue to obtain food and other support until weaning (Sullivan et al., 2000).”

What the sources say

• Not checked yetcites Sullivan et al., 2000 source

In the paper

“Hunger for comfort foods and increased caloric intake are one result, along with depressed mood and cognitive impairment (Dallman, 2003;McEwen, 2006).”

What the sources say

• Not checked yetcites Dallman, 2003 source
• Not checked yetcites McEwen, 2006 source

In the paper

“Whereas catecholamines can increase pro-inflammatory cytokine production, glucocorticoids are known to inhibit this production (Sapolsky et al., 2000).”

What the sources say

• Not checked yetcites Sapolsky et al., 2000 source

In the paper

“Effects of early maternal care are transmitted across generations by the subsequent behavior of the female offspring as they become mothers, and methylation of DNA on key genes appears to play a role in this epigenetic transmission (Weaver et al., 2004).”

What the sources say

• Not checked yetcites Weaver et al., 2004 source

In the paper

“For allostatic load, bears preparing to hibernate for the winter eat large quantities of food and put on body fat to act as an energy source during the winter (Nelson, 1980).”

What the sources say

• Not checked yetcites Nelson, 1980

In the paper

“What this non-linearity means is that when any one mediator is increased or decreased, there are compensatory changes in the other mediators that depend on time course and level of change of each of the mediators.”

In the paper

“The brain is the key organ of the stress response because it determines what is threatening and, therefore, potentially stressful, and also controls the behavioral and physiological responses, and resulting lifestyle, discussed earlier in this article, which are as important to development of allostatic load and overload as the stressful experiences themselves (Fig. 1).”

In the paper

“The effects include elevated evening cortisol, insulin and blood glucose, elevated blood pressure, reduced parasympathetic activity and elevated levels of proinflammatory cytokines, as well as the gut hormone, ghrelin, which increases appetite.”

What the sources say

• Not checked yetcites Dallman, 2003 source
• Not checked yetcites McEwen, 2006 source

In the paper

“Early life maternal care in rodents is a powerful determinant of life-long emotional reactivity and stress hormone reactivity and increases in both are associated with earlier cognitive decline and a shorter lifespan (Francis et al., 1999; Cavigelli and McClintock, 2003).”

What the sources say

• Not checked yetcites Francis et al., 1999 source
• Not checked yetcites Cavigelli and McClintock, 2003

In the paper

“Regarding the mechanism of structural remodeling, adrenal steroids are important mediators of remodeling of hippocampal neurons during repeated stress, and exogenous adrenal steroids can also cause remodeling in the absence of an external stressor.”

In the paper

“Chronic restraint stress is known to reduce dentate gyrus proliferation whereas acute restraint does not have any measurable effect (Pham et al., 2003).”

What the sources say

• Not checked yetcites Pham et al., 2003 source

In the paper

“Emotional arousal for a rodent by being placed in a novel environment is required for adrenal steroids to enhance object recognition memory, that involves the hippocampus; the effects of adrenal steroids on this memory show an inverted U shaped dose response (Okuda et al., 2004).”

What the sources say

• Not checked yetcites Okuda et al., 2004 source

In the paper

“For neurogenesis in dentate gyrus, elevated glucocorticoid levels in an enriched environment or during physical activity are associated with increased neurogenesis and/or cell survival, even though there are other conditions in which glucocorticoids suppress neurogenesis (Mirescu and Gould, 2006).”

What the sources say

• Not checked yetcites Mirescu and Gould, 2006 source

In the paper

“Excitatory amino acids released by the mossy fiber pathway play a key role in the remodeling of the CA3 region of the hippocampus, and regulation of glutamate release by adrenal steroids may play an important role (McEwen, 1999).”

What the sources say

• Not checked yetcites McEwen, 1999 source

In the paper

“there is also adaptive structural plasticity, in that new neurons continue to be produced in the dentate gyrus throughout adult life, and CA3 pyramidal cells undergo a reversible remodeling of their dendrites in conditions such as hibernation and chronic stress (Popov et al., 1992; Popov and Bocharova, 1992; McEwen, 1999).”

What the sources say

• Not checked yetcites Popov et al., 1992
• Not checked yetcites Popov and Bocharova, 1992
• Not checked yetcites McEwen, 1999 source

In the paper

“these receptors mediate a biphasic response to adrenal steroids in the CA1 region although not in the dentate gyrus (Joels, 2006)”

What the sources say

• Not checked yetcites Joels, 2006

In the paper

“These studies indicate that only more prolonged treatment by higher glucocorticoid doses are able to impair performance on more demanding tasks involving hippocampal function and that they do so under conditions in which there is no neuronal loss but there are reductions in volume of hippocampal neuropil that may be due to loss of glia cells or reduction of dendritic length and branching.”

In the paper

“In childhood, individuals with an allele of the monoamine oxidase A gene are more vulnerable to abuse in childhood and more likely to themselves become abusers, and to show antisocial behaviors compared to individuals with another commonly occurring allele (Caspi et al., 2002).”

What the sources say

• Not checked yetcites Caspi et al., 2002 source

In the paper

“With respect to stress, certain types of acute stress and many chronic stressors suppress neurogenesis or cell survival in the dentate gyrus, and the mediators of these inhibitory effects include excitatory amino acids acting via NMDA receptors and endogenous opioids (Gould et al., 1997).”

What the sources say

• Not checked yetcites Gould et al., 1997 source

In the paper

“BDNF +/− mice show a less branched dendritic tree and do not show a further reduction of CA3 dendrite length with chronic stress, whereas wild-type mice show reduced dendritic branching (Magarinos, McEwen, unpublished).”

What the sources say

• Not checked yetcites Magarinos, McEwen, unpublished

In the paper

“Neural cell adhesion molecule (NCAM) and its polysialated-NCAM (PSA-NCAM), as well as L1 are expressed in the dentate gyrus and CA3 region”

What the sources say

• Not checked yetcites Sandi, 2004 source

In the paper

“These effects occur in the medial and central amygdala and not in basolateral amygdala”

What the sources say

• Not checked yetcites Matys et al., 2004 source

In the paper

“and enhances amygdala-dependent unlearned fear and fear conditioning (Conrad et al., 1999)”

What the sources say

• Not checked yetcites Conrad et al., 1999 source

In the paper

“a large number of reported rapid, non-genomic actions of adrenal steroids (Borski, 2000; Makara and Haller, 2001)”

What the sources say

• Not checked yetcites Borski, 2000 source
• Not checked yetcites Makara and Haller, 2001

In the paper

“the discovery of adrenal steroid receptors that are G protein coupled in the amphibian brain (Orchinik et al., 1991)”

What the sources say

• Not checked yetcites Orchinik et al., 1991 source

In the paper

“Tissue plasminogen activator (tPA) is an extracellular protease and signalling molecule that is released with neural activity and is required for chronic stress-induced loss of spines and NMDA receptor subunits on CA1 neurons (Pawlak et al., 2005).”

What the sources say

• Not checked yetcites Pawlak et al., 2005 source

In the paper

“early life stress produces a delayed effect that reduces cognitive function and the number of CA3 neurons as well as decreased branching of hippocampal pyramidal neurons (Brunson et al., 2001; Brunson et al., 2005).”

What the sources say

• Not checked yetcites Brunson et al., 2001 source
• Not checked yetcites Brunson et al., 2005 source

In the paper

“whereas CRF in the central amygdala is involved in control of behavioral and autonomic responses to stress, including the release to tPA that is an essential part of stress-induced anxiety and structural plasticity in the medial amygdala (Matys et al., 2004).”

What the sources say

• Not checked yetcites Matys et al., 2004 source

In the paper

“BDNF and corticosteroids appear to oppose each other – with BDNF reversing reduced excitability in hippocampal neurons induced by stress levels of corticosterone (Hansson et al., 2006).”

What the sources say

• Not checked yetcites Hansson et al., 2006 source

In the paper

“amygdala volume has been reported to increase in the first episode of depression, whereas hippocampal volume is not decreased (MacQueen et al., 2003; Frodl et al., 2003).”

What the sources say

• Not checked yetcites MacQueen et al., 2003 source
• Not checked yetcites Frodl et al., 2003 source

In the paper

“both mild cognitive impairment and Type 2, as well as Type 1, diabetes are recognized as risk factors for dementia (Ott et al., 1996; de Leon et al., 2001; Haan, 2006).”

What the sources say

• Not checked yetcites Ott et al., 1996 source
• Not checked yetcites de Leon et al., 2001 source
• Not checked yetcites Haan, 2006 source

In the paper

“there are a variety of other anxiety-related disorders, such as post-traumatic stress disorder (PTSD) (Bremner, 2002) (Pitman, 2001) and borderline personality disorder (Driessen et al., 2000), in which atrophy of the hippocampus has been reported”

What the sources say

• Not checked yetcites Bremner, 2002 source
• Not checked yetcites Pitman, 2001 source
• Not checked yetcites Driessen et al., 2000 source

In the paper

“businesses that encourage healthy lifestyle practices among their employees are likely to gain reduced health insurance costs and possibly a more loyal workforce (Aldana, 2001; Pelletier, 2001; Whitmer et al., 2003).”

What the sources say

• Not checked yetcites Aldana, 2001 source
• Not checked yetcites Pelletier, 2001 source
• Not checked yetcites Whitmer et al., 2003 source

In the paper

“Because of the non-linearity of the systems of allostasis, the consequences of any drug treatment may be either to inhibit the beneficial effects of the systems in question or to perturb other systems that interact with it in a direction that promotes an unwanted side effect.”

In the paper

“Thus basic education, housing, taxation, setting of a minimum wage, and addressing occupational health and safety and environmental pollution regulations are all likely to affect health via a myriad of mechanisms.”

In the paper

“poor self esteem has been shown to cause recurrent increases in cortisol levels during a repetition of a public speaking challenge in which those individuals with good self esteem are able to habituate, i.e., attenuate their cortisol response after the first speech (Kirschbaum et al., 1995).”

What the sources say

• Not checked yetcites Kirschbaum et al., 1995 source

In the paper

“Having a positive outlook on life and good self esteem appear to have long-lasting health consequences (Pressman and Cohen, 2005)”

What the sources say

• Not checked yetcites Pressman and Cohen, 2005 source