Psychoneuroimmunology Epi 6181, University of Ottawa Monika Goetz Monday March 9 th,

Outline Defining PNI Defining stress The Nervous System The Immune System PNI Response 2

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) 3

Defining Stress “Nonspecific response of the body to any demand made upon it” (Hans Selye, 1979) 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) 4 Alarm High energy Resistance Alertness and healing Exhaustion Low energy

The Nervous System 5 Nervous System (NS) Central NSBrainSpinal CordPeripheral NSAutonomic NSSympathetic NS Parasympathetic NS Somatic NS

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 6

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) 7

2. The HPA Axis: Chronic Stress CRF: corticotrophin-releasing factor (or hormone) ACTH: adrenocorticotropic hormone Cortisol: “stress hormone” elevates blood sugar and boosts metabolism 8 Hypothalamus: signals pituitary gland Pituitary gland: endocrine gland (secretes hormones) Adrenal cortex: endocrine gland

The Brain and the HPA Axis Hippocampus: critical for memory storage Amygdala: important for emotion processing Paraventricular nucleus: a part of the hypothalamus 9

Key Stress Messengers Catecholamines Epinephrine (E), norepinephrine (NE) Produced by adrenal gland as well as postsynaptic sympathetic neurons Act on adrenic receptors Response to acute stressors Promotes production of pro- inflammatory cytokines Glucocorticoids Cortisol Produced by adrenal gland in response to ACTH (part of HPA Axis) Act on glucocorticoid receptors For adaptive purposes Regulates production of pro- inflammatory cytokines 10

The Immune System Innate Immunity Rapid response (hours) Reacts the same way for every kind of infection Uses physical and chemical barriers Phagocytic cells, blood proteins Adaptive Immunity Slower response (days) Increases strength and specificity with each repeated infection Uses white blood cells, macrophage cells, antibodies 11

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 12

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 13

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 14

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 15

PNI 16

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! 17

References 1. Black, Paul H., “Stress and the inflammatory response: A review of neurogenic inflammation”, Brain, Behavior, and Immunity 16, 622– Hamer, M., Endrighi, R., and L. Poole, “Physical Activity, Stress Reduction, and Mood: Insight into Immunological Mechanisms” Psychoneuroimmunology: Methods and Protocols, Methods in Molecular Biology, vol Jones, Harlan P., “Immune Cells Listen to What Stress is Saying: Neuroendocrine Receptors Orchestrate Immune Function”, Psychoneuroimmunology: Methods and Protocols, Methods in Molecular Biology, vol Kalat, James W., “Biological Psychology 10 th Edition”, Wadsworth, Cengage Learning 5. McEwen, Bruce S., “Physiology and Neurobology of Stress and Adaptation: Central Role of the Brain” Physiol Rev 87: 873– McCorry, Laurie K., ”Teacher’s Topics: Physiology of the Autonomic Nervous System” American Journal of Pharmaceutical Education; 71 (4) Article Smith, Sean M., and Wylie W.. Vale, ”The role of the hypothalamic-pituitary-adrenal axis in the neuroendocrine reponses to stress”, Dialogues Clin Neurosci. 2006;8:

Thank you for listening 19