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STRESS AND THE BRAIN
by Prof Santy Daya
Faculty of Pharmacy, Rhodes University, South Africa
Stress is a word which was originally only used by engineers to describe unbalanced forces when building bridges. It was introduced into medicine in the 1920's by Selye who used the word to describe the ability of the brain to cope with workload and emotional turmoil. Stress refers to the amount of perceived "pressure" that we experience in the face of various situations, challenges, etc. Such stress depends on the amount of perceived ability we bring to each situation and task.
The lower our sense of perceived efficacy and empowerment, the more sense of stress we feel. The higher our sense of self control, the lower the sense of
stress. It is always an inside experience. Like Beauty, it is in the eye of the
beholder. It has a structure that we can model and replicate in the same way as Eustress,
for example, motivation and challenge.
The stress response as we know it now in humans and animals, was more essential in primitive times and did not evolve with the passage of time. During stress, the adrenal glands release epinephrine, which increases the heart rate as well as blood pressure and at the same time also provides much needed glucose to the muscles which become prepared for exertion. This characteristic response is also known as the "Fight or Flight" response. In modern man, this stress response now precipitates in the office environment when confronted with major decisions. During such chronic stress, in addition to epinephrine being secreted, the adrenal glands also secrete glucocorticoids. These glucocorticoids ultimately cause damage of the hippocampus in the brain, the area known to store short term memory. Such damage by glucocorticoids can be prevented by neuroprotective agents such as melatonin.
Melatonin is a natural hormone produced by the pineal gland at night, in the absence of
light. Disruption of sleep cycles experienced during jetlag or by shift workers,
affects the daily production of melatonin. Simply putting on a bright light in
the night will immediately stop the release of melatonin. We have shown that the endogenously produced neurotoxin, quinolinic acid, can damage hippocampal neurons.
If however, melatonin is simultaneously administered along with quinolinic acid,
it prevents such damage to the hippocampal neurons. Melatonin has been shown to be a potent free radical scavenger.
Free radicals are molecules with excess energy which can cause irreparable
damage to cells and neurons. Free radicals are viewed by many as one of the
leading causes of neurodegeneration.
Melatonin synthesis by the pineal declines with an increase in age. Thus, the protective effect of melatonin is slowly lost, making organs such as the brain more vulnerable to attack by free radicals. The brain weighs approximately 1300g yet consumes about 20% of the oxygen we breathe. Thus there is a great deal of oxidation taking place in the
brain, and it is during oxidation that many free radicals are produced. The resultant free radicals lead to formation of lipid peroxides in the membranes of the neurons, causing structural damage of the neurons. At the same time, the brain has little in the way of self defense mechanisms to protect itself from free radical attack.
Diseases such as Alzheimer's and Parkinson's are neurodegenerative diseases in which there is a massive loss of neurons. Whilst there are numerous theories surrounding the cause of the neurodegeneration, the neurons ultimately die as a result of free radical attack. Results from our laboratory have shown that melatonin is able to reduce free radicals not only by being a free radical scavenger but also by binding to metal ions including, iron and copper.
Metals such as iron and copper are known to produce free radicals in certain
circumstances. So, melatonin's binding of such metal ions could potentially reduce the generation of free radicals by
what is known in biology as the Fenton reaction. Furthermore, we have shown that melatonin is also able to bind to aluminium.
Aluminium has been shown to be present in high concentrations in brains of patients who have died of
Alzheimer's disease. Whilst there is considerable debate as to whether aluminium is a causative agent of
Alzheimer's disease or whether it is an opportunist in the disorder, simply gaining access to the brain in view of a compromised blood brain barrier, it remains a fact that if aluminium is introduced into the brain, it can mimic many of the structural changes observed in
Alzheimer's disease. Thus melatonin could be the agent responsible for clearing
aluminium from the brain. With an increase in age and the associated decline in melatonin, aluminium could accumulate in the brain.
Considering stress, free radical damage and neurodegeneration, daily supplementation with melatonin could be an option to delay such disorders and the ageing process.
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