The Cybernetics of Stress: Causes, Chemicals, Consequences Richard W. Fardy, M.Ed. Wilmington High School Wilmington, MA Relevant National Standards Content Standard C: As a result of their activities in grades 9-12, all students should develop an understanding of: 1. 2. 3. 4. The cell Biological evolution Matter, energy, and organization of living systems Behavior of organisms Relevant Standards from the Massachusetts Curriculum Frameworks (Health) Standard 5: “Students will acquire knowledge about emotions and physical health,…and will learn skills to promote self-acceptance, make decisions and cope with stress.” Relevant Standards from the Massachusetts Curriculum Frameworks (Biology 9-10) Structure and Function of Cells: 2.1: Relate cell parts/organelles to their functions. Human Anatomy and Physiology: 4.2: Describe how the functions of individual systems within humans are integrated to maintain a homeostatic balance…. Evolution and Biodiversity: 5.1: Explain how comparative anatomy…and other evidence support the theory of evolution. Juggling and Authentic Learning A juggler must simultaneously integrate sensory and muscular circuitry to keep all the objects in the air. Source: http://office.microsoft .com/clipart http://office.microsoft.com/clipart Juggling and Authentic Learning (cont.) In order for learning to be truly authentic, learning experiences need to show connections to real life. Events do not always occur in a series of compartmentalized and disconnected boxes but still maintain connections to one another in some way and manner. Link to Learn The raison d’etre for both interdisciplinary instruction and conceptual linkage within a particular subject area Source: http://office.microsoft .com/clipart http://office.microsoft.com/clipart Module Objectives To be able to explain what happens in the three stages of the general adaptation syndrome (GAS). To be able to identify the parts of a neuron and explain how neurons transmit messages. To be able to define cybernetics and its connection to the nervous and endocrine systems. To be able to define homeostasis, allostasis,and allostatic load, and explain the effects of stress on homeostatic equilibrium. Module Objectives (continued) To be able to describe the essential components of a biological feedback loop and to explain the differences in the effects of negative and positive loops. To describe the psychological, neurological, and endocrine events that occur when anorexia nervosa results from stress. To be able to describe how population density induces stress in animals and the possible implications for humans. Module Objectives (continued) To be able to explain the integration of the nervous and endocrine systems in the stress response. To describe the general anatomy of the brain based on a sheep brain dissection. To be able to explain how conditioning and learning may be accomplished in planaria and how stress may affect this process. Ancient Proverb I hear and I forget. I see and I remember. I do and I understand. ∼Confucius Source: www.ironordeal.com/clipart/persons/Confucius.htm. Hans Selye (1907-1982) Proposed general adaptation syndrome (GAS) GAS theory first published in Nature in 1936 Described as body’s adaptive response to stress Just What Exactly Is Stress? Initially identified by Selye as “noxious agents.” Became known as stress syndrome. Source: www.alnoorhospital .com/uploadedfiles uploadedfiles/common/stress/jpg /common/stress/jpg www.alnoorhospital.com/ Selye’s Three Stages of Stress Stage 1: The alarm reaction in which the body prepares itself for “fight or flight.” Stage 2: Since the first stage cannot long be sustained, there is a general resistance to the stress which is established. Stage 3: If the stress is continued for a long period of time, then eventual exhaustion results (the body’s response to prolonged “wear and tear”). Selye’s Final Analysis Stress includes both internal and external factors. Factors involve the “nonspecific response of the body to any demand." The “Fight or Flight” Response 1. 2. 3. Perceive extreme danger or distress Neurons (nerve cells) in brain send entire body into “high gear” Responsively prepare for “fight or flight” Source: www.saludparati .com/entres entres..htm www.saludparati.com/ Selye’s Third Stage Challenged by physiological, psychological, and environmental changes (stressors) Failure to accommodate to changes can lead to exhaustion Source: www.bet.com/Health/Archives What Are Neurons? Neurons are the specialized cells of which nerve tissue is composed. Neurons have the ability to send “messages” to each other through the release of chemical substances called neurotransmitters. Neurons are also electrical in nature, maintaining polarity through electrical gradients established by ions on the inside and outside of their cell membranes. Neurons send electrical signals (action potentials) by depolarizing. What Do Neurons Look Like? Nerve smear containing neuron, axon, dendrite, cell body, nucleus, and nucleolus Source: http://facstaff.bloomu.edu/jhranitz/teaching/APHNT/Laboratory%20Pictures.htm Neurons labeled with fluorescent proteins Source: Joshua Sanes, Sanes, Harvard University. Lecture:” Lecture:”Neurons: how they look and what they do.7/11/2005 What Are the Principal Parts of a Neuron? A typical neuron consists of a soma or cell body where the nucleus is located, an axon which carries an impulse (action potential) away from the soma, and dendrites which carry information to the soma. Neurons interconnect by synapses (spaces over which neurotransmitters relay a message from one neuron to another). Source: http://psych.hanover.edu/Krantz/neurotut.html How an Action Potential Moves over the Neural Membrane As the previously polarized nerve cell membrane becomes depolarized, the action potential coming from the dendrites to the cell body moves toward the synaptic junction. Source: http://www.miracosta .cc.ca.us/home/sfoster sfoster/neurons/action. /neurons/action.htm htm http://www.miracosta.cc.ca.us/home/ How Do Neurons Communicate? Neurons do not physically touch each other. Neurons communicate with one another through various neurotransmitters released from synaptic vesicles at the synaptic cleft The synaptic cleft separates one neuron from another. Source:http://www. miracosta.cc.ca.us/home/ .cc.ca.us/home/sfoster sfoster/neurons/animat /neurons/animat Source:http://www.miracosta ion.gif. Perception of Pain Perception of pain by nociceptors Two types of nerve fibers involved: “A” fibers (rapidly activated) “C” fibers (activated more slowly) 1. 2. Source: www.acay.com.au/~mkause/fear%20helplessness/JPG “Good” and “Bad” Pain “A” Fibers: Signal “good pain” Serve as injury warning Release glutamate “C” Fibers: Signal more diffuse, chronic pain Pain sources include tissue damage and cancer Release “substance P” Source: http://office.microsoft .com/clipart http://office.microsoft.com/clipart A Computer-Brain Analogy Remember when the older computers didn’t have enough memory (RAM) to support more complex programs? Continual bombardment of the brain by stress signals results in the inability to process and respond adequately to such signals. Source: http://office.microsoft .com/clipart http://office.microsoft.com/clipart What Is Cybernetics? Cybernetics sounds like either robot or computer jargon but actually refers to the study of communications and control systems in biological, mechanical and electronic systems. Here, of course, we are only concerned with its biological applications (primarily in the nervous and endocrine systems). Homeostasis State of internal constancy or equilibrium necessary to maintain physiological health Disrupted by stress Source: http://spwb .com/articles/anti-aging/stress.gif http://spwb.com/articles/anti-aging/stress.gif Disturbance of Homeostasis Our bodies react to environmental changes (stressful or otherwise) by producing hormones and neurotransmitters. These chemical substances are the messengers and mediators of the nervous system and endocrine system. Stressful events cause the release of adrenalin and hormones (e.g., cortisol) from the adrenal medulla and cortex, respectively. Then What Are Allostasis and Allostatic Load? Since environmental conditions constantly fluctuate, allostasis refers to maintaining homeostasis despite these changes. Likewise, allostatic load refers to Selye’s notion of “wear and tear” that results from the inefficiency of those messenger and mediator processes over time. Allostasis and Allostatic Load Source: www.sciencebob .com/lab/bodyzone bodyzone/brain/html /brain/html www.sciencebob.com/lab/ Brain integrates and coordinates bodily responses Physiological and behavioral stress responses result in allostatic adaptation Over time allostatic load accumulates and can cause disease, even death Physiological Feedback Loops Essential components of a feedback loop: A sensory receptor sensitive to a disruptive stimulus An afferent transmission pathway A control center (i.e. the brain) serving and integrative input/output function An efferent (motor) pathway An effector to respond to the stimulus Function of Feedback Loops Negative feedback loops tend to maintain homeostasis (allostasis) by negating the effects of the disruptive stimulus. Positive feedback loops enhance the disruptive stimulus and (in most instances) are harmful. Unrelenting cycling of a POSITIVE feedback loop will result in death. Psychological Preoccupation Becomes Physiological in Anorexia In a 1977 study published in the New England Journal of Medicine, researchers showed diminished degradation of plasma cortisol and low plasma triiodothyronine (active hormone controlling metabolic rate) in young women suffering from anorexia nervosa. Psychological Preoccupation Becomes Physiological (cont.) 1. 2. The researchers concluded that anorexia involves the following cyclical sequence of events: A psychological event resulting in preoccupation with weight; Food avoidance leading to an adaptive “starvation reaction” with elevated cortisol levels mobilizing stored liver glycogen to increase blood glucose; Psychological Preoccupation Becomes Physiological (cont.) 3. 4. 5. Elevated blood glucose level leading to further loss of appetite; Diminished levels of triiodothyronine levels from the thyroid gland inducing a protective or adaptive hypometabolic state (in response to the self-imposed starvation conditions); and Resulting positive feedback loops (in the absence of timely medical intervention) promote adverse effects, even death. Some Cautionary Tales from Animal Studies In ancient Etruscan and Roman civilizations a kind of fortune-telling ritual called haruspicy was practiced. As a part of this ritual, the entrails (especially the liver) of animals were examined by the haruspex in order to predict the future. Ironically, examination of the liver and other internal organs can enable today’s pathologists to see not the future but the past. Two stress-related animal studies illustrate this point. Population Crowding Causes Stress in Deer In the early 1920’s, a pair of deer was placed on a 150-acre island in Chesapeake Bay. The deer population grew until the density reached about one deer per acre. Then the deer began to die off (in the absence of known predators) despite the presence of adequate food and water. Source: www.whiskersinn.com/sale/images/3%20deer.jpg The Post-mortem Findings On autopsy the dead deer were found to have areas of atrophy in the liver tissue, marked decrease in liver glycogen, and hypoglycemia. There was evidence of small (petechial) brain hemorrhages and both congestion and hemorrhage of the adrenal glands and kidneys. These findings suggested what later was identified as adrenal stress syndrome. Stress in Minnesota Jack Rabbits In a 1939 study also reported in The Bulletin of the Atomic Scientists, Minnesota Jack Rabbits demonstrated rise and fall in population densities but when death rates and densities were high, they frequently entered into convulsive seizures or comatose states. Liver and adrenal pathology, as well as hypertension and hypoglycemia associated with adrenal stress syndrome, were observed. Source: http://homestudy.ibea.com/wildlifeID/043jackrabbit.htm Population Density and Behavior (Norway Rats) In 1962, John Calhoun (of the National Institutes of Health) observed high mortality rates in confined wild Norway rats when population densities were high as a result of stress-induced behavioral changes. Source: http://www.ratbehavior .org/Aggression.htm htm http://www.ratbehavior.org/Aggression. Population Density and Behavior (Norway Rats) Calhoun conducted several experiments involving both a quarter-acre enclosure and 6’ x 6’ interconnecting pens. Calhoun made the following observations: Source: http://office.microsoft .com/clipart http://office.microsoft.com/clipart Behavior changes in females 1. 2. 3. Pregnancies were often aborted through miscarriage. Considerable disruption of normal pre- and postpartum maternal behavior (i.e., failure to build proper nests, nurse offspring and transport litters) occurred. Up to 25% of estrus females were so vigorously pursued by males that they did not survive. Behavior changes in males 1. 2. 3. 4. Some animals became hyperactive, constantly fighting. These animals also became hypersexual and lost the ability to discriminate among estrus and non-estrus females, juveniles, and other males. Some became cannibalistic. Some became withdrawn, demonstrating no interest in social interaction. Human Population Density The following slide depicts human population growth in Europe from an estimated number of 20 million people in 400 BC to 728 million in 2000 AD. Note that in the last three centuries or so, the growth curve becomes progressively exponential or logarithmic. Source: http://wps http://wps..prenhall.com prenhall.com Population Density and Stress in Humans Very few studies directly correlate stress of crowding with changes in the human brain. Compelling evidence now available to link neurological changes in human brains to prolonged exposure to general stress. Source: www.spokane7.com/… =Jan2004 www.spokane7.com/…/archive/asp?mon /archive/asp?mon=Jan2004 Population Density and Stress in Humans (cont.) These neurological changes may very well be connected with behavioral changes as well. For example, crime (which represents a form of social pathology) occurs at higher rates in urban than suburban areas, but the studies show mixed, non-linear correlations above certain density levels. This may be due to “self-treatment” by some individuals who feel “crowding stress” when moving to less densely populated areas (Regoeczi, 2002). Population Density and Stress in Humans (cont.) However, the cages of Calhoun more closely resemble the stressful environments of crowded prisons and concentration camps. Yet even under these conditions, there does not seem to be direct linear correlation between levels of crowding and levels of violence (Brooks, 2004). Human physiological changes seem to be much more closely linked to animal models than behavioral ones, although some degree of extrapolation seems reasonable. Stress, Hormones, and the Brain Once perceived, stress activates the hypothalamus of the brain, triggering a cascade of hormones through the hypothalamic-pituitary-adrenal (HPA) axis. Trigger of the HPA axis results in the release of glucocorticoids (e.g., cortisol) from the adrenal gland. Stress, Hormones and Brain: The Hypothalamic-Pituitary-Adrenal Axis Some neurons in the hypothalamus produce corticotropin-releasing factor (CRF). The synapses of these cells make contact with blood vessels, sending CRF to the adenohypophysis (anterior pituitary) The pituitary then secretes adrenocorticotrophic hormone (ACTH) causing glucocorticoid release by the adrenal cortex. At the same time the adrenal Source:www.aafp.org/afp/20000901/1119_f2.gif. medulla produces adrenalin. Source:www.aafp.org/afp/20000901/1119_f2.gif. (The American Academy of Family Physicians) What do glucocorticoids (such as cortisol) do? Glucocorticoids increase blood glucose for the “fight or flight” reaction and thus have short-term benefits. Over time, frequent release of these glucocorticoids adversely affects the hippocampus of the brain (the center of numerous glucocorticoid receptors). Normal levels of these steroids maintain normal neuronal function in the hippocampus, High levels of these steroids, however, adversely affect synaptic transmission and actually interfere with glucose uptake by neurons. Resultant reduction of neural connections may responsively induce memory loss (Seckl, 2005). Daily changes in cortisol in depressed patients Source: Neuroscience Presentation by Paul Arfydio, Harvard University. July 14, 2005 Jonathan Seckl’s Conclusions 1. 2. 3. 4. Both animals and humans may gradually develop a stress-related syndrome involving: Excess levels of glucocorticoids Pathological changes in the structure and function of hippocampal cells Neuronal death (sometimes) Increased numbers of hippocampal glucocorticoid receptors, making the brain more sensitive to negative feedback control. This may be one mechanism of action for certain antidepressant drugs. Laboratory Activity: Identifying the Brain’s Basic Machinery Perform a dissection of the sheep (Ovis) brain according to the excellent guide presented in the following link to the University of Scranton Neuroscience Program Dissection Guide: Sheep Brain Dissection Guide Learning and Conditioning in Planaria (Dugesia sp.) The planarian worm (Dugesia) is a small, freeliving (i.e. non-parasitic) flatworm belonging to the phylum Platyhelminthes. The planarian worm is acoelmate (without a body cavity enclosing the gut). The planarian worm has a nervous system with 2 lightsensitive eyespots, cephalic ganglia (“brain”), and 2 parallel longitudinal, ventral nerve cords. Source: www.anselm www.anselm..edu/ edu/…/genbios/surveybi04.html Learning and Conditioning in Dugesia (cont.) Materials: Culture of live Dugesia Plastic training maze 6V lantern battery and bell wire Camel’s hair artist’s brush Learning and Conditioning in Dugesia (cont.) Protocol: Separate the Dugesia into two groups: control and experimental. Place the control animals at the beginning of the Tmaze and allow them to move through it randomly. This will leave a layer of mucus on the maze and facilitate movement by others. Note the numbers which move left, straight ahead, or right when they reach the maze intersection. If they are reluctant to move at all, then gentle prodding with a soft brush may be helpful. Learning and Conditioning in Dugesia (cont.) Now repeat the process with the experimental group: This time apply an electric shock to the water, surrounding any worm which moves either straight ahead or to the right. Repeat the experiment over a week’s time in order to observe and record the success of the learning process. Learning and Conditioning in Dugesia (cont.) One variant of this experiment involves . . . Keeping the animals in the dark and then exposing them to a bright light as an electrical shock is administered to the water; Then determining the number of trials required for the worms to recoil as though they were receiving an electrical shock when exposed only to the light source. Observing the Effects of Stress on Learning in Dugesia Worms conditioned to light exposure experiment (and presumably stressed after repeated trials) Comparatively tested against previously trained T-maze worms to determine possible relationship between stress of prior conditioning and performance in new trials References Boyer, R.M.,et al. Cortisol secretion and metabolism in anorexia nervosa.NEJM, 294 (4),1977. Brooks, Crystal. Overcrowding and violence in federal correctional institutions:An empirical analysis. Retrieved from http://dspace.library.drexel.edu. Bresler, Jack B., ed. Human Ecology. Reading,MA. AddisonWesley.1966. Calhoun, John. Population density and social pathology. Scientific American. Feb.,1962. References (continued) Cox, Thomas. Black Hills State University. Learning and Conditioning Laboratory. PSYC305L. Fall, 2004. Retrieved from http://www.bhsu.edu. Duane, Mary, et al. Inquiry in science using an animal behavior model. Retrieved from http://www.woodrowwilson.org/teachers/bi/1998/planaria/index.ht m. Hoagland, Hudson. Cybernetics of population control. Bulletin of the Atomic Scientists. Feb.,1964. Marieb, Elaine N. Essentials of Human Anatomy and Physiology. San Francisco. Addison-Wesley-Longman. 2000. References (continued) Massachusetts Department of Education. Massachusetts Curriculum Frameworks. Retrieved from http://www.doe.mass.edu/frameworks. Mayer, Emeran A. The neurobiology of stress and emotions. Participate/Digestive Health Matters.Winter, 2001. McEwen, Bruce and Teresa Seeman. Allostatic load and allostasis. Retrieved from http://www.macses.uscf.edu/Research/allostatic/notebook/allostatic. August, 1999. National Institute of Child Health and Human Development. NIH Backgrounder. http://www.nichd.nih.gov. Sept. 9, 2002. References (continued) National Research Council and National Academy of Sciences. National Sciences Education Standards. Retrieved from http://www.nap.edu/readingroom/books/nses/html/index.html. Regoeczi, Wendy C. The impact of density: The importance on nonlinearity and selection on flight and fight response. Social Forces. 81, 2002. Retrieved from http://www.ncsociology.org/sociationtoday/v22/crowding.htm. Seckl, Jonathan R. Glucocorticoids, aging, and nerve cell damage. Retrieved from http://neuroendo.org.uk/index/php/content/view/18/11. June, 2005. Society for Neuroscience. Brain Facts, a Primer on the Brain and Nervous System. Washington. Society for Neuroscience. References (continued) Spedding, M. and P. Lestage. Synaptic plasticity and neuropathology: New approaches in drug discovery. MedSci (Paris). 21:1. Jan., 2005. United States Dept. of Agriculture. Agricultural Research Service. Detecting stress in animals. Agricultural Research. Jan.,2002. University of Scranton Neuroscience program. “Welcome to the Sheep brain Dissection Guide.” Retrieved from http://www.humboldt.edu. Module Assessment Questions 1. Describe how the general adaptation syndrome (GAS) may have evolved as an adaptation for survival. 2. What kinds of environmental changes induce stress in animals? In people? 3. What are the main parts of a neuron, and how do neurons work? 4. What are synapses, and how do they operate? How would neurons be different if they were directly connected (like soldered electrical wires)? Module Assessment Questions (II) 5. 6. 7. 8. How is pain perceived, and what makes it a stressor? Distinguish between the perception of “good” and “bad” pain. What evidence exists to show that high population density can induce stress? What changes are induced in the brain and hormonal system as a result of stress? What are the components of a feedback loop? Distinguish between the effects of negative and positive feedback loops. Module Assessment Questions (III) 9. 10. 11. 12. Distinguish between allostasis and allostatic load. What similarities and differences exist between humans and animals in how they respond to stress? How would you account for both the similarities and differences? What is the hypothalamic-pituitary-adrenal (HPA) axis, and how does it operate? What kinds of chemical substances are involved in the perception of stress and stress responses? How do they work?