When studying identical twins, researchers can sift through such questions, says Plassman. If a disease is purely driven by genetics, then when one twin develops the disease, the other twin will be stricken as well. Plassman’s team combed through data collected by the National Academy of Science and National Research Council, which brought together a large cohort of male World Word II veterans, all of whom were identical twins. In February of 2000, Plassman and her colleagues reported that while genetics accounts for much of the occurrence of Alzheimer’s Disease, it can’t explain everything. Other factors were at play, and Plassman’s group has since been looking into whether the disease could be contingent on subtle medical conditions, occupational characteristics, or physical activity levels.
Following suit, a research group led by Mark Tuszynski at the University of California, San Diego, has turned to studying non-human primates, in an effort to explore how different environments might affect the development of the disease. In the January 2011 issue of the Neurobiology of Aging, the team reported a striking association: the size of an animal’s cage, and perhaps the subsequent stress endured by the animals in smaller enclosures, may influence how animals’ brains diminish as they get older. By cataloging the effects of early life experiences on future brain health, researchers may begin to stratify the non-genetic components of cognitive decline and Alzheimer’s Disease progression, discerning whether stress casts its own foreboding shadow on the brain.
In Tuszynski’s study, one group of monkeys, the control group, was raised in standard-sized cages. Another set was raised in cages that were too small for the monkeys to get adequate exercise, and as confirmed by other primate studies, tend to stress the animals, elevating the levels of glucocorticoid hormones circulating through their bodies.
Stress-related glucocorticoids – cortisol in primates and corticosterone in rodents – have been shown to reduce the number of synapses, altering the way brain cells communicate with each other. Several areas of the brain have receptors for glucocorticoids, which may explain how these hormones make their mark on neurons.
Using special proteins that adhere to specific structures in the brain, Tuszynski’s team measured the relative number of synapses, as well as the amount of sticky amyloid plaques that formed in each monkey, both of which are persistent hallmarks of cognition, and frequently used to classify Alzheimer’s Disease. Monkeys raised in smaller cages had, on average, a higher density of plaques and lower number of synapses, the same brain pathology seen postmortem in Alzheimer’s patients.
More or less, all of the primates raised in normal size cages had the same amount of plaque. The monkeys housed in smaller cages as youngsters, on the other hand, had much more variation in their plaque level, suggesting stress may affect individuals in different ways. For some, it’s detrimental, while others appeared to take it in stride.
Clearly, these results only provide a correlative link between early life experience and measures of cognitive function, a retrospective peek that implies stress may be more than an emotional burden. But, as Plassman pointed out, we don’t know whether the brain changes the authors observed translated into true cognitive slips. Tuszynski’s team reported that they were simply not able to run tests on cognitive function for this particular experiment, because some of the older monkeys were brought to them just a few weeks before they died.
While a causal link between stress and Alzheimer’s Disease remains elusive, a bevy of research has shown that moderate stress can in fact make the symptoms of neurodegenerative diseases worse – not just in Alzheimer’s, but in animal models of Parkinson’s Disease, too.
In March 2010, a research team run by Karim Alkadhi at the University of Houston used an “at-risk” model of Alzheimer’s, where doses of amyloid peptides – the same molecules that form the plaques seen in patients – were injected into rats, but at levels much too low to cause any symptoms. The researchers then stressed some of the animals by placing an intruder rat into their home cage, a model which had previously demonstrated a substantial increase of corticosterone in the rats’ bloodstream. By splitting the rodents into four groups, the team was able to tease out whether the sub-clinical dose amyloid peptides and stress treatments worked independently, or in concert, to make the animal’s cognitive abilities worse.
The researchers determined how well each group of rats could learn and remember a new task, by hiding a platform from view in a rodent water maze. Usually, after a few tries, a rat will remember where the platform is located, and have no trouble swimming to it on subsequent days. Only one group had difficulty learning the new task (and remembering where it was located): the animals that received both the amyloid dose and were regularly stressed out. Alkadhi’s results show that chronic stress alone doesn’t alter long-term memory. Similarly, putting an animal at-risk for Alzheimer’s by dosing them with amyloid peptides, does not affect how well they learn. But chronic stress seems to push the at-risk animals over the edge, making them less likely to learn, and remember, new things.
Whereas Alzheimer’s Disease is marked by neurodegeneration in the areas of the brain responsible for memory and general cognitive function, patients suffering from Parkinson’s Disease primarily have motor difficulties, since they lose specialized brain cells that produce dopamine, a chemical essential for voluntary movement. But despite the differences in pathology and symptoms, studies conducted by Gerlinde Metz’s lab at the University of Lethbridge have shown that underlying stress may hasten the disease just the same.
To create a rat model of Parkinson’s Disease, Metz’s team induced a chemical lesion in rats’ brains by infusing a toxic, cell-killing drug into an area rich with dopamine neurons. Additionally, some of the animals were subjected to chronic stress by placing them in a Plexiglas tube for 20 minutes every day during the weeks of the experiment, a procedure known to temporarily elevate the rats’ level of stress hormones. A third group of rats received direct injections of corticosterone, which consistently kept the animals’ stress hormones elevated during the experiment. Getz’s team then used a battery of behavioral tests, including a skilled reaching exercise, where the rats had to slip their paws through a narrow opening in a test chamber, to assess the animals’ motor functions.
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4 Comments
Add CommentHaving recently developed Parkinson's I have been reading up on brain function, and this article dovetails nicely with other information. I hope that parents, teachers and administrators read this article because the stress that many students experience from parental pressures, academic standards and peer bullying or ostracism are likely having long term consequences for the students and for society.
Reply | Report Abuse | Link to thisThank you for the article. Positive news on gloomy conditions, at long last.
Reply | Report Abuse | Link to thisThat corticosteroids as well as adrenaline wreak damage on all organs of the body is obvious. Their purpose is to initiate the emergency response protocols which allow us to defend against or escape from imminent danger by activating the body's "afterburner" mechanisms. However, since Jurassic times, the survival of most land animals rarely depends on their remaining in constant 24/7 "battle mode", which by very definition, cannot possibly be done without damaging DNA. The human body, having evolved the intelligence to foresee and avoid mortal threat, thus is individually responsible for the amount of stress that it encounters. There can be no denying that a wanted criminal or a common denizen of a resource poor civilization suffers far greater stress than, say, the average Canadian. Highly educated and experienced people tend to handle conflicts without resorting to stressful confrontation or short-sighted solutions, and not surprisingly, suffer lower rates of dementia (resulting purely from neurological damage through stress induced corticosteroid exposure). Confinement in a restricted space, literally or figuratively, if known to be a major source of stress, should be outlawed. Zoos, full-time employment, neckties, government by the "ignorant and emotionally unstable" masses and marriage included.
Reply | Report Abuse | Link to thisHarmony with yourself is the answer to the problems of the mind and body that many suffer from in this society, to train yourself in positive thinking will help to clear the mind and body and bring about a state of harmony. Also compassion for others, be it be organic or inorganic matter.
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