An Analysis of the Biochemical Mechanisms of Stress in the Brain

An Analysis of the BiochemicalMechanisms of Stress in the Brain Charlotte Wenk

Abstract: Any stimulus, external or internal, that causes a biological response is known as stress, and the compensatory responses to these stresses are known as stress responses. This article will elaborate on what the stress response is, and what occurs neurochemically and hormonally throughout the brain and body during the stress response. Introduction: When a sequence of events consisting of an external or internal stimulus that causes a reaction in the brain, it then activatesaphysiologicalfightorflightsystem in the body.1 This fight or flight system is commonly known as the stressresponse. Psychological, physiological, and physical, stressors all activate biological stress responses; the biological stress responses involve the release of hormones in the systemic circulation and within central and peripheral tissues. Stress Hormones: The stress response consists mainly of three hormones, norepinephrine and epinephrine, and cortisol. The sympathetic nervous system or SNS releases norepinephrine and epinephrine (as well as adrenaline and noradrenaline) from the adrenal medulla.2 Cortisol is induced by the adrenal gland in the zona fasciculata after the hypothalamicpituitary-adrenal axis or HPA is activated.

1Dhabhar, Furdaus S., and Bruce S. Mcewen. "Acute Stress Enhances while Chronic Stress Suppresses Cell-Mediated Immunity." Brain, Behavior, and Immunity, vol. 11, no. 4, Dec. 1997, www.sciencedirect.com/science/article/abs/pii/ S08 89159197905080. Accessed 16 May 2020.

2Dhabhar, Firdaus S. "The Short-Term Stress Response – Mother Nature's Mechanism for Additionally, the HPA axis is responsible for releasing neuropeptides and hormones in the spinal cord, medulla, pons, and higher order centers like the hypothalamus. (See Fig. 1)3 Almost every cell in the body has receptors for cortisol, norepinephrine and epinephrine. These receptors induce changes in cells and tissues throughout the entire body and inform them about the presence of the given stressor.

(Fig 1) Internal Stimuli: Psychological stressors, or stress due to hypothetical events that are not physically occurring, are primarily processed by the limbic system (see Fig. 2), including the hippocampus, amygdala and prefrontal cortex. Both the hippocampus and the amygdala are rich in receptors for cortisol. Amygdala stimulation can provoke the bed nucleus of the stria terminalis to cause the release Corticotropin-Releasing

Enhancing Protection and Performance Under ConditionsofThreat,Challenge,and Opportunity." NCBI, 26 Mar.2018, www.ncbi.nlm.nih.gov/pmc/articles/PM C596 013/. Accessed 16 May 2020.

3 Ibid

Hormone or CRH. CRH then causes the adrenal gland to release epinephrine & cortisol.4 The hippocampus is responsible for the intrusive thoughts and memories that occur when one is presented with psychological stressors or internal stimuli. The prefrontal cortex is responsible for the behaviors that occur due to the stressor.

(Fig. 2) External Stimuli: Conversely, physical stressors are not processed, at least fully, in the limbic system. Stress caused by physical factors cause the rapid activation of the SNS and the HPA axis. This, in turn, regulates the release of glucocorticoids (GCs) from the HPA axis. GCs mediate numerous physiological and metabolic reactions which prepare one to deal with the stressful situation. However, the process to form GCs from CRH hormones is very complex.5

4 Chrousos,G.P.,andP.W.Gold."TheConcepts of Stress and Stress System Disorders. Overview of PhysicalandBehavioralHomeostasis."nih.gov,8July 1992, pubmed.ncbi.nlm.nih.gov/1538563/. Accessed 16 May 2020. The Formation of Glucocorticoids: CRH is not only prevalent with Psychological stressors, CRH is the major physiological activator of the HPA axis. It coordinates the neuroendocrine response to stress. CRH is released from parvocellular neuroendocrine neurons of the paraventricular nucleus of the hypothalamus (PVN). These neurons release CRH into the hypophyseal portal vasculature (blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus with the anterior pituitary). The hypophyseal portal system transports CRH to secretory corticotrope cells in the anterior pituitary. The cells in the anterior pituitary gland then express the CRF receptor type 1. The activation of CRFR1 stimulates the release of Adrenocorticotropic hormone (ACTH) and other pro-opiomelanocortin (POMC) derived peptides. Finally, ACTH, triggers the synthesis and release of GCs from the adrenal cortex.6

(Fig. 3)

5Dedic, Nina, et al. "The CRF Family of NeuropeptidesandtheirReceptors-Mediatorsof the Central Stress Response." nih.gov, 11 Feb. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC593045 3/ #r19. Accessed 16 May2020.

6 Ibid

Functions and Effects of

Glucocorticoids: The GCs mediate numerous physiological and metabolic reactions and ultimately prepare the organism to deal with the stressful situation. These responses to GCs affect many bodily systems. For example, the musculoskeletal system, as stress causes muscletension. Stress also affects the respiratory system. Stress causes shortness of breath and rapid breathing (hyperventilation). Stress also affects the cardiovascular system; Adrenaline, noradrenaline and cortisol causes an increase in heart rate and stronger contractions of the heart muscle. And, the blood vessels that direct blood to large muscles dilate. This increases the amount of blood pumped to specific parts of the body and elevates blood pressure. The gastrointestinal system is affected as the brain-gut communication is affected by stress. Millions of bacteria inhabit the gut

i Chrousos,G.P.,andP.W.Gold."TheConceptsof Stress and Stress System Disorders. Overview of PhysicalandBehavioralHomeostasis."nih.gov,8July 1992, pubmed.ncbi.nlm.nih.gov/1538563/. Accessed 16 May 2020. Dedic, Nina, et al. "The CRF Family of NeuropeptidesandtheirReceptors-Mediatorsof the Central Stress Response." nih.gov, 11 Feb. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC593045 3/ #r19. Accessed 16 May2020. Dhabhar, Firdaus S. "The Short-Term Stress Response – Mother Nature's Mechanism for Enhancing Protection and Performance Under ConditionsofThreat,Challenge,and Opportunity." NCBI, 26 Mar.2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC596401

3.

7 Stresseffectsonthebody."AmericanPsychological Association, 2020, www.apa.org/helpcenter/stressbody. Accessed 16 May 2020. which influence its health and the brain’s health. The changes in gut bacteria can influence mood and emotions. Stress can cause, acid reflux, heartburn, bloating, nausea, stomach pain, vomiting, change in appetite, diarrhea, constipation. All of these possible symptoms are due to that stress affects every aspect and every organ in digestion. 7GCs also restore the HPA axis to its normal state after the body has reacted to the stressor. GCs signal back via glucocorticoid (GR) and mineralocorticoid receptors (MR) which reside in the cytoplasm of cells. The GRs and MRs mediate the genomic actions of GCs by acting as nuclear transcriptional activators and repressors. Membrane bound GRs mediate the rapid actions of GCs which consequently halts the secretion of CRF and then ACTH. (See Fig 3.) 8

i

Accessed 16 May 2020 Dhabhar, Furdaus S., and Bruce S. Mcewen. "Acute Stress Enhances while Chronic Stress Suppresses Cell-Mediated Immunity." Brain, Behavior, and Immunity, vol. 11, no. 4, Dec. 1997, www.sciencedirect.com/science/article/abs/pii/ S08 89159197905080. Accessed 16 May 2020. Srinivasan, Subhashini, et al. "The role of the glucocorticoids in developing resilience to stress and addiction." Frontiers in Psychiatry, 1 Aug. 2013, www.frontiersin.org/articles/10.3389/fpsyt.2013.000 68/full. Accessed 16 May 2020. "Stresseffectsonthebody."AmericanPsychological Association, 2020, www.apa.org/helpcenter/stressbody. Accessed 16 May 2020.

8Srinivasan, Subhashini, et al. "The role of the glucocorticoids in developing resilience to stress and addiction." Frontiers in Psychiatry, 1 Aug. 2013, www.frontiersin.org/articles/10.3389/fpsyt.20 13.00068/full. Accessed 16 May 2020.