From the standpoint of survival and health of the individual, the most important feature of mediators associated with allostasis is that they have protective effects in the short run. However, they can have damaging effects in the long run if there are many adverse life events or if hormone secretion is poorly regulated as in a sustained allostatic state that leads to allostatic overload. We shall now illustrate how the immediate effects of the secretion of mediators of allostasis such as glucocorticoids and catecholamines are largely protective and adaptive.
We then note the damaging consequences that result from overproduction and/or dysregulation of the same mediators. Glucocorticoids, so named because of their ability to promote conversion of protein and fats into usable carbohydrates, serve the body well in the short run by replenishing energy reserves after a period of activity such as running away from a predator. Glucocorticoids also act on the brain to increase appetite for food and to increase activity and food seeking behaviour, thus regulating behaviours that control energy intake and expenditure.
This is very useful when we have to run several miles, but it is not beneficial when we grab a bag of potato chips while sitting at our desk and working on a computer. Inactivity and lack of energy expenditure creates a situation where chronically elevated glucocorticoids can impede the action of insulin to promote glucose uptake. One of the results of this interaction is that insulin levels increase. High insulin and glucocorticoid concentrations promote the deposition of body fat. This combination of hormones also promotes formation of plaques in coronary arteries.
Free living animals responding to storms, change in social status, or human disturbance that result in reduced access to resources such as food and shelter increase glucocorticoid secretion to facilitate foraging and promote gluco-neogenesis (generating glucose in the liver). There is also an inhibition of processes not essential for survival (e.g., reproduction), an increase in activity associated with moving away from the perturbation or finding shelter, and promotion of night restfulness with a saving in energy.
Glucocorticoids act in concert with chemicals in the central nervous system, to orchestrate these complex physiological and behavioural re-sponses to perturbations of the environment. For the heart, we see a similar paradoxical role of allostasis mediators. Our blood pressure rises and falls during the day as physical and emotional demands change, providing adequate blood flow as needed. Yet, repeatedly elevated blood pressure resulting from additional allostatic load promotes generation of atherosclerotic plaque, particularly when combined with a supply of cholesterol, lipids, and oxygen-free radicals that damage the coronary artery walls.
Beta-blockers’ are known to inhibit this cascade of events and to slow down the arteriosclerosis. Thus, despite their short-term adaptive roles, catecholamines and the combination of glucocorticoids and insulin can have dangerous effects on the body.
The nervous system interprets which events are ‘stressful’ and determines behavioural and physiological responses to the stressor, and it shows a similar paradoxical action of the mediators of allostatic load. In the brain, strong emotions frequently lead to ‘flashbulb’ memories, e.g., where we were and what we were doing when we heard of Indira Gandhi’s assassination, the horrible events of 11 September 2001, or remembering the location and events associated with a very positive life event like proposing marriage or receiving a promotion or award. Both catecholamine receptors and these blood pressure lowering drugs are commonly called beta-blockers though the correct scientific term is beta-adrenergic receptor blockers.
Glucocorticoids play an important role in establishing these long lasting memories. A number of brain structures participate along with the autonomic nervous system. A section of the brain called the amygdala plays an important role in this type of memory. It is aided by the autonomic nervous system, which picks up a signal from circulating epinephrine, and by the hippocampus, which helps us remember ‘where we were and what we were doing’ at the time the amygdala was turned on in such a powerful way. Thus, epinephrine and glucocorticoids promote the memory of events and situations, which in future may be dangerous. This is an adaptive and beneficial function.
The paradox for the brain comes when there is repeated stress over many days or when allostatic load forces gluco-corticoid levels to remain high. Then there is atrophy of brain cells and inhibition of ongoing regeneration of nerve cells. After very prolonged periods of allostatic load, allostatic overload may occur and neurons may actually die. Through some or all of these processes, the hippocampus (a portion of the brain) undergoes a shrinkage in size, with impairment of declarative, contextual, and spatial memory.
This can be picked up in the human brain by neuropsychological testing accompanied by Magnetic Resonance Imaging (MRI) in such conditions as recurrent depressive illness, Cushing’s syndrome, post-traumatic stress disorder, mild cognitive impairment in aging, and schizophrenia.