IB 139 Lec 7 Autonomic Nervous System and Allostasis

  1. What does cortisol do in GC signaling?
    • Sits around in plasma with carrier protein
    • Enters cell through membrane
    • Binds to GR
    • Changes its conformation
    • HSP90 dissociates
    • NLS visible now
    • NLS makes GR's dimerize
    • Travels to and enters nucleus
    • Binds to glucocorticoid responsive element on DNA at DNA binding domain
    • Helps with transcription and activates gene expression
  2. What is the hypothesis for genetically manipulating GC signaling with 11-beta HSD?
    • 11-beta HSD will degrade cortisol into cortisone
    • Wont' bind to GR
    • GR won't enter nucleus
    • Nothing happens
  3. What is the hypothesis for genetically manipulating GR signaling by using a GRbeta instead of GRalpha?
    • dominant negative GR will antagonize GR
    • Cort will bind to GR but dimerizes with dnGR, so nothing happens
  4. What happens when there's a high amount of estrogen in the hippocampus?
    High estrogen protects the hippocampus
  5. How does high estrogen protect the hippocampus?
    • Increases neuronal survival of necrotic insult
    • Enhances dendritic sprouting and synapse formation
    • Strengthens Long Term Potentiation (LTP)
  6. What is the hypothesis for genetically manipulating GR signaling with ER/GR?
    • ER/GR will eliminate cort effects, and mimic estrogen
    • Cort enters cell
    • Binds to both GR and ER/GR
    • ER/GR dimerizes
    • ER/GR dimer enters cell but binds to estrogen responsive element (ERE) instead of GRE
    • Activates estrogen responsive gene expression
  7. Summarize the three genetic manipulations of GC's signaling
    • Inactive metabolite: Corticosterone enters cell; interacts with 11-beta HSD to make 11-dehydrocorticosterone; doesn't bind to GR
    • Dominant negative: Corticosterone enters cell; binds to form GR/GRbeta dimer; doesn't go into nucleus
    • Convert response: Corticosterone enters cell; binds to ER/GR; enters nucleus; binds to ERE; activates estrogen responsive gene expression
  8. How would you get certain engineered proteins into brain cells?
    • New genetic material
    • Use either virus or stem cells
    • Inject into brain
  9. How are vectors neuroprotective?
    • Vectors protect against cell death in epilepsy
    • Vectors protect against stress effects on stem cells in the hippocampus
    • ER/GR expression enhances spatial memory performance and blocks the impairing effects of GCs on such performance
    • ER/GR chimera protects against stroke-induced cell death, blocks fear memory consolidation
  10. What is the normal fight or flight stress response pathway?
    • Stressful signal
    • HPA axis
    • Increases heart rate, blood pressure, and blood flow to muscles
  11. What is the short term stress pathway?
    • Stress signal in hypothalamus
    • Nerve impulses to spinal cord
    • Preganglionic sympathetic fibers to adrenal medulla
    • Catecholamines released (epinephrine and norepinephrine)
  12. What is the long term stress pathway?
    • Stress signal in hypothalamus
    • CRH (corticotropin-releasing hormone)
    • Corticotrope cells of anterior pituitary
    • ACTH released
    • To target in blood
    • Adrenal cortex
    • Mineralocorticoids (MC) and Glucocorticoids (GC) released
  13. Describe the roadmap to neuroanatomy.
    Image Upload 1
  14. What is the autonomic nervous system (ANS)?
    • Division of the peripheral nervous system
    • Influences the function of internal organs
  15. What are some of organ functions that the ANS influences?
    • Heart rate
    • Digestion
    • Respiratory rate
    • Pupillary response
    • Urination
  16. What are the 2 divisions of the ANS?
    • Sympathetic
    • Parasympathetic
  17. What is the parasympathetic division generally responsible for?
    Rest and digest
  18. What kinds of thingds does the parasympathetic division do?
    • Constricts pupil
    • Stimulates saliva production
    • Constricts bronchi
    • Slows heart
    • Stimulates stomach, pancreas, and intestines
    • Stimulates urination
    • Promotes erection of genitals
  19. What is the sympathetic division generally responsible for?
    Fight or flight
  20. What kinds of things does the sympathetic division do?
    • Dilates pupils
    • Inhibits saliva production
    • Dilates bronchi
    • Accelerates heart
    • Simulates epinephrine and norepinephrine release
    • Stimulates glucose release
    • Inhibits stomach, pancreas, and intestines
    • Inhibits urination
    • Promotes ejaculation and vaginal contractions
  21. What hormones does the adrenal medulla release?
    • Adrenaline (aka epinephrine)
    • Noradrenaline (aka norepinephrine)
  22. Which amino acid are adrenaline and noradrenaline derived from?
  23. What is the splanchnic nerve?
    Neurons that are part of the sympathetic branch of the nervous system
  24. The adrenal medulla is innervated by which nerve/set of neurons?
    Splanchnic nerve
  25. What happens when the splanchnic nerve is stimulated following a physical or mental stress?
    Chromaffin cells in the adrenal medulla release adrenaline (80%) and noradrenaline (20%) into the blood stream
  26. What do the hormones adrenaline and noradrenaline bind to in the blood?
    • Adrenergic hormones
    • Transmembrane proteins in the plasma membrane of many cell types
  27. What are adrenergic receptors?
    • Transmembrane proteins in the plasma membrane of many cell types
    • Class of G protein-coupled receptors
    • Targets of the catecholamines, especially noradrenaline and adrenaline
  28. Associated nerves and prevertebral ganglia send out what kind of fibers?
    Sympathetic fibers
  29. Associated nerves and terminal ganglia send out what kind of fibers?
    Parasympathetic fibers
  30. What are chromaffin cells?
    • Neuroendocrine cells in the adrenal medulla
    • Release adrenaline and noradrenaline in response to neural input
  31. The binding of a catecholamine to an adrenergic receptor will generally stimulate which nervous system?
    Sympathetic nervous system
  32. What are the effects of adrenaline and noradrenaline?
    • Increae in heartbeat (resulting in increased blood pressure)
    • Blood shunted from the skin and viscera to the skeletal muscles, coronary arteries, liver, and brain
    • Rise in blood sugar
    • Increased metabolic rate
    • Bronchi dilate
    • Pupiles dilate
    • Hair stands on end (goosebumps)
    • Increased ACTH secretion from the anterior lobe of the pituitary
  33. What is the longer pathway for the fight or flight stress response?
    • Stress signal
    • Hypothalamus
    • Stimulates splanchnic nerve
    • Stimulate adrenal medulla
    • Release adrenaline and noradrenaline from chromaffin cells
    • This is all short-lasting though
    • Either go directly to muscles and get response (high BP, muslces, etc.) or go to HPA axis then the muscles
  34. Adrenaline and NE effects are immediate, and ___________?
  35. What is allostasis?
    • Maintianing stability (or homeostasis) through change
    • The process of achieving stability, or homeostasis, through physiological or behavioral change
  36. When does an allostatic sttate occur?
    When set-points vary outside homeostatic limits and results in an imbalance of the primary mediators
  37. How can allostasis be carried out?
    • By means of alteration in:
    • HPA axis hormones
    • The autonomic nervous system
    • Cytokines
    • Or a number of other systems
  38. Allostasis is generally adaptive in the ____-term.
  39. Why is allostasis essential?
    In order to maintain internal viability amid changing conditions
  40. Who made the term allostatic load?
    McEwen and Stellar (1993)
  41. What is allostatic load?
    • The physiological cost of making long-term adaptive shifts across a broad range of systems to match internal functioning to environmental demand
    • 'The cost of adaption'
    • The wear and tear to the body systems that result from maintenance of allostatic changes over a long period
  42. What is homeostasis?
    The regulation of the body to a balance, by single point tuning
  43. What are examples of homeostasis?
    • Blood oxygen level
    • Blood glucose
    • Blood pH
  44. What's an example of the body maintaining homeostasis with body temp?
    • When walking through a hot desert, the body will sweat
    • They will quickly become dehydrated
  45. How is allostasis different from homeostasis in regards to the desert/dehydration example?
    • Allostasis is adaption but in regard to a more dynamic balance
    • In dehydration, sweat occurs as only a small part of the process
    • Many other systems are also adapting their functioning, to reduce water use and to support the variety of other systems that are changing to aid this
    • Kidneys may reduce urine output, mucous membrane in the mouth, nose and eyes may dry out
    • Urine and sweat output will decrease
    • The releae of vasopressin (AVP, or ADH) will increase
    • Veins and arteries will constrict to maintain blood pressure with a smaller blood volume
  46. What is allostatic overload?
    Pathological condition that could develop
  47. Every system in the body responds to acte challenge with what?
  48. What results from acute challenges becoming chronic?
    Allostatic overload
  49. What's the point of allostatic load resulting from acute challenges turning chronic?
    • Nothing, serves no useful purpose
    • Just predisposes individuals to disease (overload)
  50. What are the different types of allostatic load?
    • Frequent activation of allostatic systems
    • Lack of adaption to repeated stressor
    • Failure to shut off allostatic activation after stress
  51. Describe frequent activation of allostatic systems.
    Repeated hits from multiple stressors resulting in overexposure to stress hormones
  52. Describe lack of adaption to repeated stressor.
    • Lack of adaption to the same stressor
    • Ex. public speaking
  53. Describe failure to shut off allostatic activation after stress.
    • Inability to efficiently shut off stress response resulting in overexposure to stress hormones
    • Ex. Impaired negative feedback regulation of cort
    • Hippocampus malfunction in aging
    • Individual variability comes into play
  54. What does a normal physiological response to stress look like plotted?
    Gradual rise and fall
  55. What does does the stress response for repeated "hits" look like plotted?
    Normal response repeated over time, gradually decreasing in height
  56. What does the stress response for lack of adaption look like plotted?
    Repeated peaks at the same height
  57. What does the plot look like for prolonged stress response?
    • Increase
    • Then plataeu with no recovery
  58. What does the plot for inadequate stress response look like?
    Barely any increase and then a decrease back to baseline
  59. What kind of allostasis does stress induce?
    Either adaptive or maladaptive allostasis of stress mediators
  60. Stress mediators constitute what?
    • ANS (blood pressure, catecholamines)
    • Metabolic hormones (cortisol, insulin)
    • Pro- & anti-inflammatory cytokines
  61. What happens if stress stimuli are excessive and repetitive?
    • Recovery to the original homeostatic levels may be incomplete
    • Chronic stress can make a body system think the stress of new enviroments would persist
    • Demands newly defined set point for future adaption
    • Diff btwn new and old set points called 'cumulative burden of adaptation to stress'
  62. What is the difference between new and old set points for stress mediators called?
    Cumulative burden of adaptation to stress
  63. What's an example of cumulative burden of adaptation to stress?
    Allostatic load
  64. Where can examples of allostatic load be found?
    • Primary mediators
    • Secondary outcomes
    • Or tertiary outcomes
  65. What are examples of allostatic load in primary mediators?
    • Hypercortisolemia
    • Increased inflammatory cytokines
  66. What are examples of allostatic load in secondary outcomes?
    • Elevated blood pressure
    • Overweight
    • Insulin resistance
  67. What are examples of allostatic load in tertiary outcomes?
    • Hypertension
    • Diabetes
    • Obesity
    • Coronary heart disease
    • Neurodegenerative disorders
  68. What part of the physiology does the stress response affect- activation and overload?
    • Immune suppression
    • Reproductive distress
    • Digestive tract
    • Cardiovascular
    • Bone
    • Metabolism
    • Accelerated aging
  69. What happens to the physiology of the digestive tract as a result of stress response activation and overload/wear and tear?
    • Peptic ulcers
    • Decreased nutrient absorption
    • Stunted growth
    • Colitis
    • Irritable bowel syndrome
  70. What are examples of energy mobilization for gastro-intestinal tract during fight or flight response?
    • GI shuts down
    • No saliva production (dry mouth)
    • No stomach mvmt, enzyme secretion, blood flow
    • Small intestine suppressed, large intestine moves so no water re-absorption
  71. What happens to your cardiovascular system as a result of stress response activation and overload/wear and tear?
    • Atheriolosclerosis
    • Hypertension
    • Chronic myocardial ischemia
    • Sudden cardiac arrest
  72. What are examples of energy mobilization for cardiovascular system during fight or flight response?
    • Increased sympathetic and decreased parasympathetic signaling
    • Increased heart rate and cardiac output
    • Increased blood pressure (vasoconstriction)
    • Increased blood flow to brain and muscles
  73. WHat happens to your bones as a result of stress response activation and overload?
    • Stunted growth
    • Osteoporosis
  74. What happens to your metabolism as a result of stress response activation and overload/wear and tear?
    • Inefficient process; fatigue
    • GCs decrease insulin sensitivity in adipocytes, and exacerbate insulin resistance or glucose intolerance
    • Late-onset Diabetes Type II, prediabetes
  75. What are examples of energy mobilization for metabolism during flight or fight response?
    • Decreased insulin secretion
    • GC block glucose transport to adipocytes, glycogenolysis, and protein breakdown
    • All together- increased blood glucose levels
  76. The stress response is all about energy _________.
  77. What are some non-vital functions that are repressed during the response to stress?
    • Reproduction
    • Growth
    • Digestion
Card Set
IB 139 Lec 7 Autonomic Nervous System and Allostasis
IB 139 Lec 7 Autonomic Nervous System and Allostasis