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With a deadline looming and an article to finish writing, I can feel my stress levels rising. Knots of tension in the stomach, just like the last time I was close to a deadline. I hope it doesn't lead to stomach ulcers, or worse. At least I know that I am not alone in this fast, modern-day world where work-related stress is one of the major occupational health problems leading to ill health and time off work. Factor in other stress triggers like relationship problems, bereavement, ill health, unemployment and moving house and it's a wonder that we are not all quivering wrecks. It is common knowledge that stress can make you ill, inducing a variety of conditions like the aforementioned ulcers, hypertension and depression. The body produces chemicals under stressful conditions that help us to cope. For instance, adrenaline, noradrenaline and cortisol levels are increased to activate the fight-or-flight response. However, these act in the short term. Long-term stress is more difficult to deal with and tends to produce the ill effects. Currently, most research into stress has focused on taking a snapshot of the condition, examining plasma and tissue at a given point of time for molecular indicators. This on-off approach is not ideal because it does not reflect the dynamic behaviour - the effects of stress come and go - and a more representative approach is needed to fully understand its effects. One way that has been adopted recently is to take a metabonomics approach to stress and a team of scientists has demonstrated the ability of GC/MS with statistical analysis to illustrate the metabolic effects of acute cold stress and the anti-stress effects of ginsenosides on rats, which are used as models of the human condition. Now the team has extended the work to compare the metabolic changes induced by acute and chronic stress. Wei Jia and co-researchers from the Shanghai Jiao Tong University, the Shanghai University of Traditional Chinese Medicine and the University of North Carolina at Greensboro chose urine as the sampling fluid. Unlike plasma or tissue, urine can be collected in a non-invasive manner that will not lead to additional stress that might distort the results. For the acute studies, rats were exposed either to -10°C for 2 hours, or were forced to swim for 20 minutes in deep water, representing physical and physical/psychological stress, respectively. Urines from these and control animals were collected for 24 hours on days 1, 2 and 6. In the chronic stress studies, rats were treated to a different stress every day for 27 days, recycling the same 9 stresses three times. They were forced swimming (5 minutes), hot room temperature (40°C for 5 minutes), water deprivation (24 hours), food deprivation (24 hours), tail squeeze (1 minute), electric shock (10 seconds), day and night reversal, cool room temperature (-10°C for 30 minutes) and behaviour restriction (2 hours). Again, 24-hour urines were collected on several days. The urines were all derivatised with ethyl chloroformate then subjected to GC/MS and the data were subjected to multivariate statistical analysis and principal components analysis to visualise any trends present. The two types of acute stress induced similar metabolic variations along a similar path, with a distinct pre-stress starting point, followed by a marked deviation on day 1, a shift towards normal on day 2 and return to normal by day 6. Under chronic stress, clear differences were observed between the metabolic profiles after 0. 9 and 27 days, suggesting a gradual metabolic variation over time. However, the effects of both types of stress were transient, being reversible with time. When the metabolic indicators were compared, several metabolites behaved in the same way during acute and chronic stress. Glutamate, glutamine, homovanillate, proline, succinate, citrate and tyrosine all varied one way whereas pimelate and hippurate followed the opposite trend. However, different types of stressors altered the same set of metabolites in the same way, supporting the claim that the physiological responses to stress are non-specific. The chronically stressed animals displayed depression-like symptoms after 27 days of stress and this was supported by the effects on several metabolites associated with depression. These included 5-hydroxyindoleacetate, a metabolite of the neurotransmitter 5-hydroxytryptamine (5HT), and tryptophan, a precursor of 5-HT, which were both decreased. The trends found for organic acids implicated an increased disturbance of gut microbiota as stress continued, and evidence of the involvement of further biochemical pathways during chronic stress was also found. This research illustrates the ability of urinary metabolite profiling by GC/MS with statistical analysis to effect non-invasive monitoring of different metabolic pathways during stress events, which is an improvement over previous studies in which samples were collected at one time point. It could also be applied to study the effects of other stimuli on the rat that can be extrapolated to the humans and provide insight into how the metabolism is influenced. Related links:
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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