Download Monika Goetz

Psychoneuroimmunology
Epi 6181, University of Ottawa
Monika Goetz
Monday March 9th, 2015
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Outline
 Defining PNI
 Defining stress
 The Nervous System
 The Immune System
 PNI Response
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Defining PNI
 Psychoneuroimmunology: aka PNI, the study of the
relationship between the nervous system and the immune
system
 Nervous system: the network of nerve cells and fibers that
transmits nerve impulses between parts of the body
 Immune system: the network of immune cells that protect
the body through immune responses
 Stress causes the nervous system to activate the immune
system
 The two systems communicate via the endocrine system
(hormones)
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Defining Stress
 “Nonspecific response of the body to any demand
made upon it” (Hans Selye, 1979)
Alarm
Resistance
Exhaustion
• High energy
• Alertness and
healing
• Low energy
1. Sympathetic NS
2. HPA Axis
 “Events that are interpreted as threatening to an
individual and which elicit physiological and
behavioural responses” (Bruce McEwen, 2000)
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The Nervous System
Nervous System
(NS)
Central NS
Brain
Peripheral NS
Spinal Cord
Autonomic NS
Sympathetic NS
Somatic NS
Parasympathetic
NS
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1. Sympathetic NS (SNS):
“Fight or Flight”
 Brain sends signals to the sympathetic ganglion in the spinal
cord
 Presynaptic neurons secrete acetylcholine (ACh), which
binds to postsynaptic neurons, signaling release of
catecholamines (epinephrine, norepinephrine)
 Innervation found in blood vessels, liver, kidney, intestines,
lung, heart, and brain
 Results in pupil dilation, increased sweating, blood sugar,
heart rate, and blood pressure
 If stressor is prolonged, adrenal gland also secretes
epinephrine and norepinephrine
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Parasympathetic NS (PNS):
“Rest and Digest”
 Innervation in postrema (part of medulla in the
brainstem, controls vomiting) which connects to HPA
axis and activates sympathetic NS
 Operates via vagus nerve, partially reponsible for
control of the heart and digestive system
 Main neurotransmitter is acetylcholine (ACh)
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2. The HPA Axis:
Chronic Stress
CRF:
corticotrophin-releasing
factor (or hormone)
ACTH:
adrenocorticotropic
hormone
Cortisol: “stress hormone”
elevates blood sugar and
boosts metabolism
Hypothalamus:
signals
pituitary gland
Pituitary gland: endocrine
gland (secretes hormones)
Adrenal cortex:
endocrine
gland
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The Brain and
the HPA Axis
Hippocampus:
critical for memory storage
Amygdala:
important for emotion processing
Paraventricular nucleus:
a part of the hypothalamus
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Key Stress Messengers
Catecholamines
 Epinephrine (E),
norepinephrine (NE)
 Produced by adrenal gland as
well as postsynaptic
sympathetic neurons
 Act on adrenic receptors
Glucocorticoids
 Cortisol
 Produced by adrenal gland in
response to ACTH (part of
HPA Axis)
 Act on glucocorticoid
receptors
 Response to acute stressors
 For adaptive purposes
 Promotes production of pro-
 Regulates production of pro-
inflammatory cytokines
inflammatory cytokines
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The Immune System
Innate Immunity
Adaptive Immunity
 Rapid response (hours)
 Slower response (days)
 Reacts the same way for
 Increases strength and
every kind of infection
specificity with each
repeated infection
 Uses physical and chemical
barriers
 Phagocytic cells, blood
 Uses white blood cells,
macrophage cells, antibodies
proteins
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Immune Response
 Certain immune cells produce cytokines: small proteins
that combat infections and communicate with brain
 Trigger hypothalamus to produce fever, sleepiness, lack
of energy, lack of appetite, and lack of sex drive
 Ways of conserving energy, immune response is very
energy consumptive
 Inflammation result of response, good for drawing
immune cells to site of infection but can be harmful if
chronic or systemic
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Receptor-Mediated Immune
Response
 Adrenergic receptors (E and NE, SNS)
 Expressed in white blood cells
 Pro-inflammatory (alertness and healing)
 ACh receptors (PNS)
 Expressed in some immune cells
 Anti-inflammatory cytokine production
 CRH receptors (HPA Axis)
 Expressed in immune cells
 Pro-inflammatory cytokines
 Glucocorticoid receptors (Cortisol, HPA Axis)
 Expressed in immune cells
 Regulates inflammatory response by acting as a negative regulator
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Chronic Stress
 Symptoms of illness often from own body fighting off
infection, body perceives “stress” as an infection
 Overstimulation of HPA Axis shown to be
immunosuppressive
 Brief release of cortisol improves memory, attention, and
immune response – good
 Prolonged release impairs memory and immune activity –
not good
 Exhaustion – energetically expensive
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Conclusions
 Temporary or acute stress can be important in driving
our behaviours and contributing to our survival (SNS,
fight or flight)
 Chronic stress can lead to exhaustion and
immunosuppression, threatening our survival (HPA
Axis)
 Stress-related inflammation may be a significant
contributor to inflammatory diseases and risk factor
for other health problems
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PNI
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Stress Management
 Pharmaceutical agents
 Sleep medication
 Antidepressants
 Drugs that reduce inflammation and oxidative stress
 Physical activity
 Increases neurotrophin (neuron growth factor) expression in
cortex and hippocampus
 Increases neurogenesis in dendate gyrus of hippocampus
 Social support
 Eliminating stress!
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References
1.
Black, Paul H., 2002. “Stress and the inflammatory response: A review of neurogenic inflammation”,
Brain, Behavior, and Immunity 16, 622–653
2.
Hamer, M., Endrighi, R., and L. Poole, 2012. “Physical Activity, Stress Reduction, and Mood: Insight
into Immunological Mechanisms” Psychoneuroimmunology: Methods and Protocols, Methods in
Molecular Biology, vol. 934
3.
Jones, Harlan P., 2012. “Immune Cells Listen to What Stress is Saying: Neuroendocrine Receptors
Orchestrate Immune Function”, Psychoneuroimmunology: Methods and Protocols, Methods in
Molecular Biology, vol. 934
4.
Kalat, James W., 2009. “Biological Psychology 10th Edition”, Wadsworth, Cengage Learning
5.
McEwen, Bruce S., 2007. “Physiology and Neurobology of Stress and Adaptation: Central Role of the
Brain” Physiol Rev 87: 873–904
6.
McCorry, Laurie K., 2007. ”Teacher’s Topics: Physiology of the Autonomic Nervous System”
American Journal of Pharmaceutical Education; 71 (4) Article 78
7.
Smith, Sean M., and Wylie W.. Vale, 2006. ”The role of the hypothalamic-pituitary-adrenal axis in the
neuroendocrine reponses to stress”, Dialogues Clin Neurosci. 2006;8:383-395.
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Thank you for listening
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