HET301 L2: Stress models

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What is a model?

Something that reflects or describes a certain aspect of reality

Simplified with respect to the functioning counterpart integrated in the actual world

Models in biology

Itemised description of a complex system

Functional theoretical framework

Mathematical formulation of numerical relationships or statistical links

Model organisms

What is a model?

Something that reflects or describes a certain aspect of reality

Simplified with respect to the functioning counterpart integrated in the actual world

Models in biology

Itemised description of a complex system

Functional theoretical framework

Mathematical formulation of numerical relationships or statistical links

Model organisms

What is stress - classic definition

Living organisms survive by maintaining a complex dynamic equilibrium, homeostasis

internal and externalf factors threaten and disturb this state

threatened homeostasis leads to

stresss

stressor

anything that disrupts physiological balance

stress-response

the body’s attempts to re-establish balance

modern definition of stress

a condition in which a threat to the biological functions of an organism is perceived by that organism, and a set of physiological and behavioural responses is mounted to counteract this challenge

Studying stress/stress models: typical stressors in animals

Wild animals

• predators, environemtnal stress (temperature, water quality), competition

• (food scarcity and nutritional stress, parasites and disease, human disturbance)

Captivity

• Handling and transport, vaccines, social stress (crowding, agression)

• (physical environment, dietary stress, medical interventions, human interactions, sensory stressors, boredom and behavioural frustration)

The other animals of the same species can be a main stressor in both nature and captivity

Why study stress in animals?

• Physiological and behavioural mechanisms of great importance to survival

• Evolutionary conserved responses - model to explain the biological background of human diseases e.g. depression

• Concern for animal welfare is increasing

  • Affects productivity and economogy of animal rearing operations

Stress - history

• Walter Bradford Cannon

Coined the term fight or flight to describe an animal’s response to threats

The homeostasis concept

Found that also physiological emergencies evoke release of adrenaline into the bloodstream

Stress - history

Hans Selye

Stress - the nonspecific response of the body to any demand

General adaptation syndrome

Three phases: alaarm, resistance/adaptation, exhaustion

Distress and eustress

Stress - history

John Wayne Mason

Psychological influences on the pituitary-adrenal cortex system

Re-evaluation of the concept of non-specificity in stress theory

Stress - history

Robert Sapolsky

Psychosocial activation of the stress response

Social hierarchies

Effects of long-term stress

Stress - history

Bruce McEwen

Stress and the brain

The allostasis concept

Stress - history

Jaap Koolhaas

Individual stress coping styles

The physiolgoical response itself does not necessarily indicate stress

Cognitive perception of uncontrollability and/or unpredictability is the key factor

Stress should be restricted to those instances when the organism cannot respond and readjust to change

Psychological components of stress: predictability

Experiment with rats

Rat 1: put into apparatus but received no shock. Therefore the amount of stress exhibited by this rat is a measure of the stressfulness of being constrained in the test appratus

Rat 2: received a warning signal before shock

Rat 3: yoked to rat 2. Rats 2 and 3 received exactly the same number of shocks, but 3 received no warning signal before shock.

Results:

• rats in the no shock group showed a small amount of ulceration

• Rats given signalled shock had an intermediate amount of ulceration

• Rats that were unable to predict shock showed significantly greater stomach ulceration

Conclusion

• a psychological factor - predictability must be responsible for difference between these groups

Psychological components of stress: control

• Experiments with rats

Rat 1 put into apparatus but received no shock

Rat 2 could avoid and escape shock by pressing lever. Therefore this rat can use a coping response to control shock delivery

Rat 3 yoked to rat 3. Received shock when rat 2 failed to emit and avoidance or escape response. Rat 3 could not avoid or escape shock

Results

Rats in the no shock group showed a small amount of ulceration

Rats that were able to use a coping response to control shock showed an intermediate stress response

Rats with no control over shock delivery had significantlhy greater stomach ulceration thatn rats that received exactly the same amount of electric shock but were able to avoid or escape from it

Conclusin

• a psychological factor - control- must be responsible for difference between these groups

(human studies: it is not the actual control that counts, but the perceived control)

Key points

Stress level is determined by

What actually occurs, what the brain registers, what is expected occur

Predictability and control reduces stress

The synapse in action - multiple levels of control and plasticity

Synapse numbers: neural pathways - brain architecture

1. Synthesis and storage of neurotransmitter molecules in synaptic vessels

   1. Levels of precursors, enzymes to synthesize

2. Release of neurotransmitter molecules into synaptic cleft

   1. Arriving action potentials

3. Binding of neurotransmitters at receptor sites on postsynaptic membrane

   1. Receptor number and type depend on previous use, hormones etc.

4. Inactivation (by enzymes) or removal (drifting away) of neurotransmitters

   1. Enzymes to break down

5. Reuptake of neurotransmitters sponged up by the presynaptic neuron

   1. Rreuptake mechanism

Types of stress

Postiive stress

Tolerable stress

Toxic stressP

Positive stress

A personal challenge that has a satisfying outcome

Result: sense of mastery and control

Healthy brain architecture

Good self-esteem, judgement and impulse controlT

Tolerable stress

Adverse life events buffered by supportive relationships

Result: coping and recovery

Healthy brain architecture

Good self-esteem, judgement and impulse control

Toxic stress

Unbuffered adverse events of greater duration and magnitude

Result: poor coping and compromised recovery

Result: increased life-long risk for physical and mental disorders

Compromised brain architecture

Dysregulated physiological systems

The allostasis concept

Achieving stability through cahnge in anticipation of physiological requirements

Both the internal and external environemtn changes continuously in the allostasis concept

• allostasis

• allostatic load

allostasis: continuous readjustment

allostatic load: cost/magnitude of these changes

Homeostasis - definition

The stability of physiological systems that maintain life, used here to apply strictly to a limited number of systems such as pH, body temperature, glucose levels and oxygen tension that are truly essential for life and are therefore maintained within a range optimal for each life history stage

Allostasis - definition

Achieving stability through change, a process that supports homeostasis, i.e. those physiological parameters essential for life defined

Allostatic overload

Unpredictable, uncontrollable and chronic stressors accumulate so that normal adptation adn regulation fails

Possible outcomes of allostatic overload

Energy demand exceeds energy intake

problems not related to energy demand

• metabolic imbalance

• brain remodelling

• heart remodelling

• immune balance

this all leads to the inability to respond to further change and challenges → lack of coping

Enviornmental stressors engage brain systems that perceive the stressful situation, activating both behavioural respones and physiological responses

These responses can be shaped by individual differences that may arise from genetic polymorphisms or from experience (e.g. early life environment, cumulative exposures. The behavioural and physiologic responses are an integral component of allostatic responses which promote adaptation and also contribute to allostatic load. Long-term buildup of allostatic load can lead to allostatic overload and breakdown of this integrated set of responeses, promoting pathology

Living in a box - the concept of tolerance limits

Instruemnts the animal can use:

• Migration, genomic adaptation, phenotypic plasticity (acclimation)

Stress response - stress and the HPA axis

Hypothalamus - CRH

Pituitary gland - ACTH

Adrenal glands (located above kidneys) - cortisol

The hypothalamus respons to levels of cortisol

• reduces CRH if cortisol is high and increases CRH if cortisol is low

Physiological stress responses

• the allostatic mediators: sympathetic branch of the autonomic nervous system

Epinephrine (Adrenaline)

• binds to multiple receptors

• Increases heart rate and stroke volume

• Dilates the pupils

• Constricts arterioles in the skin and gut

• Increases catalyses of glycogen to gluocse in the liver

• initiates breakdown of lipids in fat cells

• Suppressive effect on the immune system

  • Cognitive effects: enhances memory formation

The hypothalamus=pituitary-adrenal (HPA) axis

Key elements of the HPA axis

• the paraventricular nucleas of the hypothalamus

  • Synthesize and secrete corticotropin-releasing hormone (CRH) and vasopressin

• The anterior lobe of the pituitary gland

  • CRH and vasopressin stimulate the secretion of adrenocorticotropic hormone ACTH

• The adrenal cortex

  • produce glucocorticoid hormones in response to stimulation by ACTH

• Negative feedback

  • Glucocorticoids act back on the hypothalamus and pituitary to suppress CRH and ACTH production

stress models

• social stress in fishes (rainbow trout)

the trout/salmon model for social dominance

physiological and behavioural effects of social rank

fights for socail dominance in territorail rainbow trout

arena: glass aquaria with removable walls

fish: juvenile (30-150 g) trout moved from group rearing to isolation

isolation for 1 week with daily access to food creates territorial fish

dominance test: removal of walls between neighbouring fish

• inactivity (10s-90m)

• aggressive displays (0.5-5m)

• fights: circling, attacks, biting (0.5-180m)

  • resolution/dominance: unilateral aggression (duration of the experiment)

Chronic stress effects in the salmon

Subordinate fish are int he periphery of the test arena

Subjected to unpredictable aggression

Reduced or completely inhibted feed intake

Completely inhbited aggressive behaviour after initial fights

Long lasting effects, even if removed from dominant individual

Chronic stress effects - rats

A stressor can be distinguished from a normal controllable situation by the recovery of the physiological response rather than the magnittidue of the response

The concept of active and passive behavioural responses to stres

Acute:

fight or flight or active coping - an active attempt to counteract the stressor may or may not be mounted

milk, predictable, controllable stressorss

Chronic

conservation-withdrawal, or passive coping; inhbition of appetite, aggression, locomotion, reproduction

Why two types of responses?

At an early stage the severity of the stressor is not know, an active attempt to counteract it , may or not may be rewarded

During severe or chronic stress, decreased risk-taking, resource conservation and a wait and see strategy is more rewarding (if you can not do anything about it, why try?)

the threshold at which the shift between active and possive coping occurs is subject to large individual variation (risk-taking strategy vs stress-coping style)

behavioural effect of stress is highly dependent on dose and duration of exposure