Friday, September 16, 2011

What is stress and how does it help us?

Let’s talk about stress.

When we think of stress, we typically think of events that challenge our comfort or happiness- things like big exams, arguments with a significant other, or financial problems. When stuff like this happens to us, we often tell people that we’re “stressed out.” But where did the word “stress” come from? Prior to the early 1900s, “stress” was a term that belonged to the lingo of engineers and physicists (think of bridges and buildings). Our current connotation of stress can be attributed to an Austro-Hungarian endocrinologist named Hans Selye.  Selye was injecting rats with various organ extracts when he noticed that regardless of what type of organ extract he used, all of his rats developed ulcers, atrophied thymus glands, and enlarged adrenal glands. It turns out that Selye was a very clumsy scientist and often dropped his rats and had to chase them around the room while he was trying to inject them. Selye realized that the constant handling, chasing, and actual injections made the rats…well… stressed. And so that’s how “stress” came to be.

But what is stress? A good, basic definition is that stress is the physiological and behavioral response to unpredictable or noxious stimuli (meaning, stress is what helps you run away from a charging llama). There are two kinds of stress: acute stress and chronic stress. Acute stress may be running away from a territorial llama, but then getting to safety and revising your walking route so you never have to pass by it again. Chronic stress may be when you have to pass by an aggressive llama two times a day, everyday for a month, in order to get to your field site and there’s no alternative route because of an electric fence. This kind of stress is more long term, and the stress of dealing with the llama bypasses the actual encounter because you spend a good part of your day just thinking and worrying about the llama (note: this is just an example, there are no aggressive large animals at my field site). I’ll talk more about chronic stress in future posts, but for now, let me discuss how the stress response works:

There are two waves to the stress response. The first wave, termed the fight-or-flight response, happens within seconds of perceiving a stressor and helps the animal take immediate action to avoid or deal with the stressor. The second wave of the stress response is slower and is mediated by glucocorticoids. In my research, I mostly focus on the physiological responses caused by the glucocorticoids, but the fight-or-flight response is important and is frequently glossed over, so let me tell you a little more about it.

OK, so say a llama charges you, do you flee or do you fight? This instantaneous response is mediated by a group of hormones called catecholamines. The two main catecholamines responsible for the fight-or-flight response are norepinephrine and epinephrine (also called noradrenaline and adrenaline). When your brain perceives something as dangerous, it activates your sympathetic nervous system (SNS). The SNS activates preganglionic sympathetic nerves that innervate the adrenal medulla (the adrenal medulla is the inner part of the adrenal gland, you have two adrenal glands that sit on top of each of your kidneys). These nerves form synapses with cells that produce norepinephrine and epinephrine (these are called chromaffin cells, each individual cell can produce only norepinephrine or epinephrine, never both).  Activated preganglionic sympathetic nerves release acetylcholine into the synapse, which causes chromaffin cells to increase their membrane conductance for Ca2+, which then causes intracellular Ca2+ to rise, which then results in exocytosis of norepinephrine and epinephrine into the bloodstream. Norepinephrine and epinephrine then circulate through the bloodstream and bind to adrenergic receptors in many different tissues (question to think about: if catecholamines are protein hormones, where do you think the adrenergic receptors are located in the target cells?). Catecholamines cause a variety of physiological effects including vasoconstriction, increase in heart rate, bronchodilation, inhibition of insulin secretion, stimulation of glycolysis in muscle cells, and increase of lipolysis in fat cells (question to think about: If a person with bee allergies gets stung, how does their EpiPen help them survive?). The net result of the fight-or-flight response is to help an animal activate their muscles (and other tissues) and to mobilize as much energy as possible so they can confront or flee their stressor.

So while your fight-or-flight response is kicking into high gear to help you flee the charging llama (let’s be real here, most of us would probably run away from a charging llama rather than try to fight it), the second wave of the stress response is getting ready to help you deal with some of the more long-term effects of the stressor. The second-wave of the stress response starts when your brain perceives a stressor and then causes increased secretion of corticotropin-releasing hormone (CRH) from the hypothalamus. CRH travels down to the anterior pituitary where it causes increased release of adrenocorticotropic hormone (ACTH). ACTH then travels through the bloodstream to the adrenal glands where it stimulates increased secretion of glucocorticoids (in humans and degus, the main glucocorticoid is cortisol, in most other animals the main glucocorticoid is corticosterone. From now on I’ll refer to cortisol and corticosterone as CORT). CORT then circulates through the bloodstream and binds to receptors in a variety of different tissues. Because CORT is a steroid hormone, most of its receptors are intracellular (although there is evidence that CORT also has some extracellular receptors). Since the majority of CORT’s actions are mediated through intracellular binding, most of the physiological actions of CORT take a long time to take effect (we’re talking at least 30 minutes, here, but many physiological changes are only seen after several hours). Increased concentration of CORT causes an amazing variety of physiological effects to take place:

  •  CORT has a permissive function (this means that they help other physiological mediators take full effect) on the action of catecholamines in the cardiovascular system. This means that CORT helps prime your flight-or-fight response for the next stressor that comes around.
  • During hemorrhage, CORT has a suppressive function on secretion of arginine vasopressin (AVP) and renin. Without CORT, your body would produce way too much AVP and renin in response to hemorrhage and you would probably die from too much vasoconstriction in the liver and heart.
  • The effects of CORT on the immune systems are very complicated. But, to generalize, CORT has mostly suppressive effects on the immune system and helps prevent over-activation of immune function (question to think about: what do you use cortisone cream for?).
  • CORT helps mobilize energy stores for quick consumption by inducing lipolysis, increasing gluconeogenesis (synthesizing glucose from amino acids and fats), making cells more resistant to insulin, and stimulating appetite.
  • High CORT concentrations can suppress the reproductive system by inhibiting release of gonadotropin-releasing hormone (GnRH) and decreasing the effects of luteinizing hormone (LH) on the gonads.

To put it all together, the second wave of the stress response helps animals recover from stressors and get prepared for new stressors. In terms of our llama escape, we can think about it this way:

After we get away from the llama, our high levels of CORT help us recover from the stressor by helping us not overdo our hemorrhaging (because there’s a chance that we may have been wounded in the stressful encounter) and stimulating our appetite so we can replenish our energy stores. Our increased CORT levels are also helping us prepare for the next llama interaction (since the llama may be searching for us as we recover) by priming our fight-or-flight response, suppressing our inflammatory response so our limbs remain movable, increasing the amount of available glucose, and getting our mind off of reproduction. Basically, the body is diverting energy from unnecessary functions to preparatory functions- after the stressor is gone your body can start to worry about storing glucose, fixing a wound, and having sex.

This was my attempt to give you a basic overview of the purpose of the stress response. Having a basic understanding of the stress response is important for understanding the aims of my research, so continue to bear with me and I’ll eventually tell you more about the degus. If you’re interested in learning more about stress, here are some suggested readings:

-For an unintimidating, highly entertaining introduction to stress and its effects on human health, you must read: “Why Zebras Don’t Get Ulcers” by Robert M. Sapolsky.
-If you’re still wondering “What is stress and how do we define it?” check out this review paper: Romero, L.M., Dickens, M.J., Cyr, N.E. (2009) The reactive scope model- a new model integrating homeostatsis, allostasis, and stress. Hormones and Behavior 55, 375-389.
-For a more in-depth overview of the fight-or-flight response, try reading pgs. 333-339 in “Animal Physiology: Mechanisms and Adaptations” by Randall, Burggren, and French.
-Want to know more about glucocorticoids? This comprehensive review has it all: Sapolsky, R.M., Romero, L.M., Munck, A.U. (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews 21, 55-89.

And here is a picture of a one-day old degu:

Baby degu!


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