The Cybernetics of Stress - Life Sciences Outreach Program

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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
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
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
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/common/stress/jpg
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.htm
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, Harvard University. 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/neurons/action.htm
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/sfoster/neurons/animation
.gif.
Perception of Pain


1.
2.
Source: www.acay.com.au/~mkause/fear%20helplessness/JPG
Perception of pain
by nociceptors
Two types of nerve
fibers involved:
“A” fibers (rapidly
activated)
“C” fibers (activated
more slowly)
“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
Source: 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
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
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/brain/html
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 stressinduced behavioral
changes.
Source: http://www.ratbehavior.org/Aggression.htm
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
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.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/…/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-pituitaryadrenal (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 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
light-sensitive eyespots,
cephalic ganglia (“brain”),
and 2 parallel longitudinal,
ventral nerve cords.
Source:
www.anselm.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
T-maze 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/inde
x.htm.

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-pituitaryadrenal (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?
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