Homeostasis

Question 1

Timing of effects

Answer 1

• sympathetic response
  
  • takes less than 2-3 seconds from receiving stressful stimulus to release of NE
• adrenal response
  
  • 20-30 seconds after Epi and NE are released from adrenal medulla
• hormonal response
  
  • ACTH, vasopressin, thyroxine release under 1 min
  • effects last hours, days, weeks

Question 2

Stages of stress

Answer 2

• alarm
  
  • starts with adrenaline release from adrenal gland and medulla
• resistance
  
  • body functions maintained but at a cost of increased energy and source consumption
• exhaustion
  
  • body’s resources are eventually depleted and body is unable to function normally

Question 3

Stress and performance

Answer 3

-stress of medium intensity is connected with optimal cognitive efficiency

Question 4

HPA axis

Answer 4

• neurons in hypothalamic PV nucleus produces CRH
• CRH acts on receptors in anterior pituitary to release ACTH
• ACTH stimulates receptors in adrenal cortex to release corticosteroids
• HPA axis activated upon stress
• chronic activation leads to increase in body weight
• negative feedback induced by increasing glucicocorticoid levels is mediated through hippocampal and hypothalamic corticosteroid receptors, which suppress CRH expression
• amygdala has excitatory effects on PVN CRH neurons

Question 5

ACTH

Answer 5

• synthesized from POMC
• POMC is a 241 aa polypeptide that is cleaved by prohormone convertase
• products include melanocortins, ACTH, and melanotrophins and B-endorphin
• point mutation in cleavage site between B-MSH and B-endorphin leads to aberrant peptide synthesis which causes obesity in humans

Question 6

Adrenal gland

Answer 6

• divided into cortex and medulla
• cortex releases hormones
  
  • gluco- and mineralcorticosteroids into circulation
• medulla releases catecholamines NE and Epi
• hormones from cortex and medulla involved in stress response

Question 7

Gulcosteroids

Answer 7

• ACTH stimulates cells in adrenal cortex to release cortisol (humans, dogs) or corticosterone (rats, mouse)
• adrenal gland shows highly organized structure with layers producing distinct hormones

Question 8

Glucocorticoid receptor

Answer 8

• intracellular receptor
• ligand must be able to cross membrane
• in absence of ligand, receptor binds to heat shock protein 90 (HSP90)
• following ligand binding, HSP90 released and receptor translocated to nucleus
• steroids receptors function as transcription factors
  
  • once in nucleus bind to specific steroid response elements on DNA which results in upregulation of anti-inflammatory genes and down-regulation of pro-inflammatory cytokines

Question 9

AVP

Answer 9

-also stimulates HPA axis

Question 10

CRH receptors in brain

Answer 10

• CRF1 - widespread in brain, especially cortex and cerebellum
  
  • high levels in anterior pituitary
• CRF2 - olfactory bulb and subcortical regions
  
  • low in pituitary

Question 11

CRH receptor knockouts

Answer 11

• CRH1 deficient mice display a chronic corticosterone deficit
  
  • impaired neuroendocrine stress response and reduced anxiety
• CRH2 mutants are hypersensitive to stress and display increased anxiety
  
  • have normal basal feeding and weight gain but decreased food intake
• CRH knockout reduces plasma ACTH and a response to restraint stress impaired in mutant mice
• adrenalectomy reduces plasma corticosterone levels and increases plasma ACTH
  
  • abolishes response to restraint stress

Question 12

Astressin-B on CRF-OE mice

Answer 12

• CRF over expression mice accumulate visceral fat and show Cushings like symptoms
  
  • also develope slope is (patches of skin without hair)
• nonselective CRF antagonist astressing-B but not astressing2-B blocks allopecia but without effect on visceral fat and cushings symptoms

Question 13

Stress testing in humans

Answer 13

• SRRs tallies of life-changing events that are assigned a value
• relationship between accumulation of stressful events and risk of mental illness (Holmes and Rahe)

-adolescent life-changing scale developed

Question 14

Animal models of stress

Physical stressors

Answer 14

• temp
• electric shock
• acoustic noise
• restraint
• vibrations
• high altitude
• light
• sleep deprivation

Question 15

Animal models of stress

Physchosocial stressors

Answer 15

• isolation of social animals
• crowding of social animals
• intruder introduced into a group
• maternal deprivation
• predator odour

Question 16

HPA axis and acute/chronic stress

Answer 16

-HPA Response usually measured by ACTH/blood cortisol

1. Acute stress
   
   • induce rapid but transient ACTH and glucocorticoid
   • systems return to basal status within minutes
2. Some stressors and genetic background can result in sustained or insufficient response
3. Repeated stress usually induces desensitization but novel stimulus induce hyper-responsiveness
4. Some stressors (severe pain) dont cause habituation but the response to novel stress is similar to observed in habituated stress

Question 17

Stress intensity

Answer 17

• low increase of corticosterone is observed after home cage change, handling and noise exposer
• moderate increase after forced swimming, restraint, and foot shock
• large increase after social defeats and sexual behaviour

-higher ACTH in footshock but higher corticosterone after forced swim

Question 18

Chronic stress in humans

Answer 18

• severe chronic stress can cause over activation of HPA axis resulting in increased and sustained levels of cortisol
• can turn into many symptoms

Question 19

Restraint stress

Answer 19

• 3-week immobilization stress (6hour/day) results in significant decrease of dendrites in hippocampus and parallel decrease in performance in radial-arm water maze
• performance and dendritic spine density was recovered after 21 days
• similar effects of stress were observed in prefrontal cortex

Question 20

Coping with stress

Answer 20

• strategy used to avoid, diminish or terminate stress

- crossing of strains of mice revealed that active coping behaviour is an X linked trait

Question 21

Stress coping in pigs

Answer 21

• Place Response test is a test of association of a place with a reward
• animals kept for 8 weeks from birth in either standard environment (no exploration) or stimulus rich environment
• environmental factors may affect stress resilience and cognitive performance
• enriching environment improves cognition performance in active pigs but less in passive pigs

Question 22

Prenatal responses to stress

Answer 22

• prenatal and early life stress can have a long lasting effect on HPA axis
• maternal care can suppress HPA activation in rat pups in aversive conditioning task

-male rats divided into groups of pup which emotional reactivity and fear novelty was increase, and pups that showed lower cortisol and emotional reactivity to novelty the group 1 life span was shorter by about 200 days

Question 23

Effect of acute psychosocial stress

Answer 23

• male rat introduced to establish colony of 3 rats (2 male, 1 female) after removal of female rat
• procure resulted in severe aggression toward the new rat
• acute stress does not alter proliferation of cells in hippocampal dentate granule cell layer nor it affects the immediate survival of cells
• short term survival and long term survival of Newley generate cells in the intruder are reduced by stress

Question 24

Stress and morphology of hippocampal neurons

Answer 24

• acute stress enhances memory
• longer stress exert negative effects
• reduced density of thin spine but not mushroom-type arrowhead spines

Question 25

Chronic stress alters cortical architecture

Answer 25

• morphological cortical neurons show asymmetry in dendritic length in some cortical areas
• chronic stress abolishes the right-left differences and reduced the total length of apical dendrites in right prelimbic cortex
• stress group animals were submitted to daily restraint stress for 6 hours/day for 3 weeks

Question 26

Chronic social stress

Answer 26

• housing 4 males and 2 female rates results in formation of hierarchy with dominant male
• subordinates show more weight loss, higher basal corticosterone, defensive wounds, and habitation of smaller enclosed chambers
• omega rats are weakest and receive most wounds

Question 27

Effects of chronic stress in rodents

Answer 27

• in unstressed animals the right mPFC is under tonic inhibition from its left counterpart
• modulatory inputs from mPFC, amygdala and hippocampus to PVN relay on BNST
• in basal conditions the parasympathetic tone predominated
• chronic stress
  
  • decreases left mPFC and hippocampus in volume
  • induced dendritic atrophy byt enlarges BNST
  • left-right hemisphere imbalance and over activation of amygdala translates into dysfunction of HPA axis
  • results in increased corticosteroid levels and sympathetic activation
  • may induce immune dysregulation and contribute to behaviours dysfunction

Question 28

BNST

Answer 28

• bed nucleus of striated terminalis
• relay site within HPA axis
• one of the most sexually dimorphic brain structure
• in men it has twice the volume of that in women

Question 29

Sleep deprivation

Answer 29

• rats kept for 10 days in sleep deprivation chamber
• allowed slow wave sleep but when entering REM, rat would be awakened
• stress connected with sleep deprivation increases feeding after 6 days of experiment
• mechanisms seem to be compensation of energy/weight loss due to lack of rest

Question 30

Stress in amphibians and reptiles

Answer 30

• stress stimulated corticosterone release in amphibians and reptiles, but effects of stress depend on reproductive state, seasons etc
• low intensity stress has beneficial effect on reproduction
• high variability in both an intensity and direction of adrenocortical response in amphibians and reptiles