PSY707 Week 3 - Nervous System & Stress (PDF)

PSY707 Week 3 Dr. AJ. Fiocco 1  Week 3 Class objectives Name and describe key components of the nervous system Name and describe two key stress-sensitive systems Describe immune system activity during acute and chronic stress Describe stress and cellular agi...

PSY707 Week 3 Dr. AJ. Fiocco 1  Week 3 Class objectives Name and describe key components of the nervous system Name and describe two key stress-sensitive systems Describe immune system activity during acute and chronic stress Describe stress and cellular aging (revisiting Selye) 2 The Nervous System 3 Central Nervous System (CNS) Image: https://www.pinterest.ca/pin/117726977736536966/ 4 Selective Overview of CNS Structures of the Forebrain Telencephalon: Cerebral cortex; Limbic system; Basal ganglia Diencephalon: Thalamus; Hypothalamus https://www.pinterest.ca/pin/117726977736536966/ 5 Selective Overview: Forebrain Cerebral cortex (neocortex) 4 lobes: frontal; temporal; parietal; occipital Prefrontal cortex (PFC): important for executive functioning and behavioral regulation Limbic System Hippocampus, amygdala, anterior cingulate cortex (ACC) Memory (HC) and emotion/fear (amygdala) Emotional control (ACC) Basal Ganglia Important for movement control, Image: https://quizlet.com/226074431/lobes-of-brain-diagram/ vigilance/attention, learning (procedural) 6 Selective Overview: Forebrain Thalamus A regulatory gateway: relays sensorial and motor information Regulates consciousness, sleep, alertness Hypothalamus Regulation of homeostasis Controls the autonomic nervous system and endocrine system Fighting, feeding, fleeing, mating, sleeping, drinking Exert effects through the pituitary gland 7 Selective Overview: Midbrain & Hindbrain Structure within the Hindbrain and Midbrain Brain stem: Contains the pons, medulla and midbrain Locus Coeruleus (NE) Substantia Nigra (Dopamine) Raphe nuclei (Serotonin) Reticular Formation 8  Selective Overview: Midbrain & Hindbrain Locus coeruleus Located in the pons Nuclei involved in physiological response to stress (produces NE) Reticular formation Bundles of nuclei Extends from hindbrain to the diencephalon Transmits information between CNS and PNS Important for attention, arousal, movement, and vital reflexes (e.g. cardiovascular control) Fight-or-Flight Response! 9 Handy model of the brain (Dan Siegel) Image: https://blog.lcs.on.ca/2019/11/15/attention-muscle-reps/ 10 The Nervous System 11  PNS: Somatic Nervous System Somatic nervous system: innervates the skeletal muscles, the skin and the sense organs Neural pathways that send signals from the brain to the periphery are efferent and those that send signals from the periphery to the brain are afferent Fight-or-flight response activates the striated (skeletal) muscles Too much stress can lead to over-activation of striated muscles, resulting in muscle pain and tension 12  PNS: Autonomic Nervous System Autonomic nervous system: innervates the body’s viscera (i.e., internal organs) through pre- and post-ganglionic neurons Viscera consists of the organs, ducts and glands, smooth muscles, and blood vessels The sympathetic branch (SNS) of the autonomic nervous system is responsible for activating the fight-or-flight responses Parasympathetic branch (PNS) is associated with rest-and-digest responses 13 PNS 14 Autonomic Nervous System Basal energy conservation/restoration vs. Energy mobilization /expenditure 15 Endocrine System A system of organs and glands that secrete hormones into the blood stream to send messages to cells and organs Endocrine system works with the sympathetic nervous system during fight- or-flight activation to reach a common outcome 16 Image: https://www.pinterest.com/pin/112167846940604950/  A Few Important Glands and their Hormones Hypothalamus Pituitary Adrenal Cortex Adrenal Medulla Corticotropin-releasing Adrenocorticotropic Glucocorticoids Epinephrine(E) hormone (CRH) hormone (ACTH) (GC)/cortisol Norepinephrine(NE) Oxytocin Thyroid-stimulating Vasopressin hormone (TSH) Beta-endorphin 17  Week 3 Class objectives Name and describe key components of the nervous system Name and describe two key stress-sensitive systems Describe immune system activity during acute and chronic stress Describe stress and cellular aging (revisiting Selye) 18  Stress Response Systems 2 important stress response systems Sympathetic-Adrenal-Medulla (SAM) Axis Hypothalamic-Pituitary-Adrenal (HPA) Axis Interconnected and independent function Timing is different SAM = Fast, within seconds and ending in minutes HPA = Slow, within minutes and lasting hours 19  FAST ACTING Cortex and Limbic SLOW ACTING SAM LC- System HPA NE Endocrine Sympathetic activation activation of Hypothalamus Release of ANS CRH/CRF Stimulates anterior pituitary gland to release ACTH Stimulates adrenal medulla to release Epinephrin and Norepinephrin Stimulates adrenal cortex to release GC (cortisol) Supports SAM activity; regulates Fight or Flight metabolism and immune; Negative feedback loop Juster et al., 2011 20  SAM Axis Hypothalamus Brain Stem [reticular formation] Autonomic Nervous System Via nerve fibers Adrenal Medulla Release adrenaline (epinephrine) and noradrenaline (norepinephrine) Physiological events (dilating pupils, increase heart rate, dilation of bronchial tubes, sweat stimulation, glucose release from liver, overall increase in metabolic rate) 21  HPA Axis Stressor Hypothalamus is alerted and secretes CRH Hypothalamus alerts the Pituitary to secrete ACTH ACTH travels through the blood and alerts the adrenal cortex Adrenal cortex secretes and releases glucocorticoids/cortisol Chain of physiological events (increase in blood glucose, increase fatty acids and amino acids in blood, increase blood pressure, immune regulation 22 Image: https://www.integrativepro.com/Resources/Integrative-Blog/2016/The-HPA-Axis Note: Cortisol is a major stress hormone that helps your body respond to stress, including the stress of illness or injury. It also helps maintain your BP, heart function, immune system and blood glucose levels. Cortisol is essential for life. 23  Rare Conditions of HPA Dysregulation Addison’s disease (aka Cushing’s disease adrenal insufficiency) Adrenal cortex produces too Caused by much cortisol – caused by autoimmune disorder years of glucocorticoid tx, or damage to the tumor on pituitary or adrenal adrenal glands gland Adrenal cortex does Symptoms: muscle not produce enough weakness, emotion cortisol dysregulation, cognitive Symptoms: muscle difficulties, high BP, infection, weakness, low BP, bone loss, bruising, truncal fatigue, appetite & obesity, buffalo hump weight loss, low blood sugar, GI disruption 24  Week 3 Class objectives Name and describe key components of the nervous system Name and describe two key stress-sensitive systems Describe immune system activity during acute and chronic stress Describe stress and cellular aging (revisiting Selye) 25  Psychoneuroimmunology (psycho=consciousness, neuro=brain, immunology=body’s defense against infection “Stress plays a role in 50% to 80% of all illness and disease” Pelletier 1977 26  The Immune System The immune system protects us from harmful antigens such as bacteria, fungi, and viruses (the invaders) Our immune system has a number of layers of defense to protect our body from these invaders. 27  The Immune System Layers of defense: Innate immune system (natural, non-specific): Defense at the level of the skin and mucous membranes; bacteria that enter the skin are engulfed by phagocytes and destroyed by natural killer cell lymphocytes. Inflammatory response may also come into play. Our first-responders Adaptive immune system (acquired, specific): takes 4-5 days to defend against a novel intruder. Once an intruder is recognized, it responds quickly in the future. Know thy enemy Importance of vaccinations 28  The Immune System White blood cells (Leukocytes): Phagocytes Lymphocytes Natural killer cells = cytotoxic, destroys invader organism as part of innate immune reaction. Helper T cells = identify invader and stimulate multiplication of Killer T and B cells, produce cytokines to alert the system Killer T cells/cytotoxic T cells = destroy invader organism by puncturing and killing the invaded cells B cells = produce antibodies (immunoglobulins; Igs) that bind to antigens Memory B and T cells = recognize and respond quickly to future invaders Antibodies = cell proteins of the immune system that recognize antigens on the pathogen and fight them. Cytokines = cell proteins that serve as a chemical alarm bell (interleukin, interferon, tumor necrosis factor) 29  Immune System Innate Immune Adaptive Immune Non-specific Specific Humoral Cellular Humoral (Th2) Cellular (Th1) Skin, mucosa, Lymphocytes (B Phagocytes, NT Lymphocytes (NK, T cytokines cells). Antibodies, cells), phagocytes cytokines Cellular-mediated immunity Humoral-mediated immunity Type 1 T-helper cell (Th1) Type 2 T-helper cell (Th2) 30  Stress and the Immune System Does stress suppress immune function?? BUT! Research shows that stress can enhance immune function!!!… the paradox 31  Stress and the Immune System Immune dysregulation: Overactive immune system can result in allergies, arthritis, and lupus; while an underactive immune system can result in cancer and cold/flu outbreaks Cortisol plays most important role in immunosuppression 32 Stress and Immune function over time…Th1:Th2 ratio Th1Th2 Th1 Th2 T Helper 1 (Th1, cellular) vs. T Helper 2 (Th2, humoral) 33  Prolonged Initial SAM activation of activation HPA and and release secretion of of NE GC 34 Examining the Relationship Between Chronic Stress and Immune Dysregulation Exam Stress Large-scale disasters Family caregiving 35  Stress and Immune Function: [Caregiver = Chronic Stress Model] Experimental, Observational Design Sample: 13 women caring for relative and 13 age- and income-matched controls Wound healing: 49 vs 39 days to heal Kiecolt-Glaser et al 1995 Lancet 36 The Caregiver: A Model of Chronic Stress? Prospective, Observational design Sample: Older spousal caregivers and non- caregiver controls (66-96 yo) Observational period: 1993 -1998 average 4.5 years of follow-up Mortality: 63% relative risk of mortality among caregivers experiencing caregiver burden Schultz and Beach, 1999, JAMA 37  Caregiver Stress & Immune Caregivers reported greater symptoms of depression Activation-induced T cell proliferation is lower in caregivers than matched controls Greater pro-inflammatory cytokine production in caregivers Telomere length of leukocytes are shorter in caregivers Damjanovic et al., (2007). J Immonul. 38  Week 3 Class objectives Name and describe key components of the nervous system Name and describe two key stress-sensitive systems Describe immune system activity during acute and chronic stress Describe stress and cellular aging (revisiting Selye) 39  Revisiting Selye “Every stress leaves an indelible scar, and the organism pays for its survival after a stressful situation by becoming a little older.” Image: https://gettingstronger.org/2011/09/voluntary-stress/selye-2/ 40 Telomeres and Telomerase Telomeres = chromosome aglets Protect the ends of chromosomes “Disposable buffers” at the end of chromosomes Telomeres shorten with cell division Telomeres are consumed during cell division and replenished by the enzyme telomerase 41 Telomeres and Mortality: Cawthon et al 1999, Lancet 42  Telomeres and Stress in Caregivers Study (Epel et al., 2004) 58 healthy mothers of a chronically ill child (n=39) or healthy child (n=19) Measures psychological distress, TL and telomerase (blood) Results: High stressed women had 50% lower levels of telomerase High stressed women had 50% lower levels of telomerase High stressed women had shorter telomeres Longer stress duration = shorter telomere length Greater Perceived stress = shorter telomere length Epel et al. 2004 PNAS 43 Telomeres and Stress Biomarkers Epel et al., 2006: Collected evening urinary hormone excretion Shorter telomeres associated with: Higher cortisol Higher norepinephrine and epinephrine 44 Stress and Telomeres Tomiyama et al 2012 45  TL is malleable! Important: TL can change over time (Epel et al., 2009 Aging, Goglin et al., 2016) Goglin et al 2016 46  Telomeres and Stress Shorter telomere length is associated with: Smoking Poor diet Greater adipose composition Increasing weight and increased insulin resistance* Lower antioxidant intake Sedentary (dose response effect) 47 Take Home Messages To understand stress, you need to understand what is going on inside the body This knowledge gives you perspective and a better understanding of how stress may impact your health If you can identify where stress shows up in the body, then you have a target to work with Chronic stress plays a significant role in a majority of poor health outcomes Chronic stress accelerates cellular aging BUT! Remember, stress is in the eye of the beholder and the relationship between chronic stress and health outcomes of malleable 48