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Stress in animals
• Mark Wilson, a neuroscientist at Yerkes National Primate Research Center of Georgia's Emory University, studies captive
female rhesus macaque monkeys, housed in groups as they would live in the wild
...
• "Subordinate females tend to show more anxiety behaviors — things like excessive body scratching, body shakes,
excessive yawning, self-grooming, pacing," Wilson said
...
• Overall, though, humans may win the "most neurotic animal" award
...
"Not to be specieistic here, but animals tend to live fairly stable lives
...
"
Examples of stress in animals
• To better understand how to combat the effects of stress in the body,
Wilson and his colleagues recently conducted an experiment with
female rats, in which they increased the amount of a neurohormone
called corticotropin releasing factor (CRF), thought to be a driving
factor of the body's response to stress, in the rats' brains
...
STRESS RESPONSE IN FISH
NEUROENDOCRINE AND PHYSIOLOGICAL
RESPONSES TO STRESS
PHYSIOLOGICAL RESPONSE TO STRESS
• Neurotransmitter response
• Endocrine response
• Immune response
A) NEUROTRANSMITTER RESPONSE TO STRESS
Stress activates
• Serotonergic system
• Noradrenergic system
• Dopaminergic system
• Amino acid and peptinergic neurotransmitter system
NEUROTRANSMITTERS RESPONSE TO STRESS
• Neurotransmitters send and receive messages between brain cells
...
• The three "happy" messengers are: Serotonin, Noradrenaline, and
Dopamine
...
Body clock coordinates your body
functions to the same rhythm
...
• Glucocorticoids themselves have myriad effects within the body, but their
actions can be summarized in the very short term as promoting energy use,
increasing cardiovascular activity (in the service of the flight-or-fight
response), and inhibiting functions such as growth, reproduction, and
immunity
...
It is
essential for life, and it regulates or supports a variety of important cardiovascular,
metabolic, immunologic, and homeostatic functions
...
• Blood sugar (glucose) levels
• Fat, protein and carbohydrate metabolism to maintain blood glucose
(gluconeogenesis)
• Immune responses
• Anti-inflammatory actions
• Blood pressure
• Heart and blood vessel tone and contraction
• Central nervous system activation
PHYSIOLOGICAL EFFECTS OF CATECHOLAMINES
Organ
Effect
Brain
Increased blood flow, increased glucose metabolism
Cardiovascular system
Increased rate and force of contractions, Peripheral vasoconstrictions
...
Liver
Increased glucose production, gluconeogenesis, glycogenolysis and decreased
glycogen synthesis
...
Skeleton
Decreased glucose uptake and utilization
GI and genitourinary tract Decreased protein synthesis
Lymphoid tissue
Increased protein breakdown
ADRENERGIC RECEPTORS
Receptor
Effectively Binds
Effect of Ligand Binding
Effect on organ
Alpha1
Epinephrine,
Norepinphrine
Increased free calcium
Cause smooth muscle to constrict
& increased glycogenolysis
Alpha2
Epinephrine,
Norepinphrine
Decreased cyclic AMP
Relaxation of smooth muscle
Beta1
Epinephrine,
Norepinphrine
Increased cyclic AMP
Increased heart rate, contractile
force and automaticity
Beta2
Epinephrine
Increased cyclic AMP
Bronchodilation and vasodilation
HYPOTHALAMIC-PITUITORY-THYROID AXIS
The hypothalamus begins the chain of command by producing a
hormone called thyroid releasing hormone (TRH) which stimulates
the pituitary to produce and release its hormone, thyroid
stimulating hormone (TSH)
...
While the entire hypothalamus-pituitary-thyroid axis is fairly
complex, TSH remains the most sensitive measure of overall thyroid
function
...
Hydrocortisone produced by adrenals is necessary for the
conversion of T4 to the active T3
Hypothyroidism
...
IMMUNE RESPONSE TO STRESS
• Recent research has shown that immune system is a key player in stress physiology
...
NEUROENDOCRINE AXIS:
• The other way in which the brain can communicate with the immune system is via the HPA system
...
• Cortisol can also prompt some immune cells to move out from circulating blood into lymphoid
organs or peripheral tissues, such as the skin
...
g
...
IMMUNE RESPONSE TO STRESS
• Autonomic Nervous System
• Sympathetic nervous system activation can reduce cellular immune response activation by
suppressing the activity of diverse populations of immune cells, including natural killer (NK) cells
and T lymphocytes
...
CHRONIC STRESS, DEPRESSION, AND IMMUNITY:
• Chronic or naturalistic stressors are associated with reliable decreases of cellular and innate
immunity
...
This latter
observation is not surprising, because individuals undergoing stress often report negative emotions
and depressive symptoms, and the presence of such affective symptoms is associated with greater
immune alterations
...
g
...
Chronic hyperactivation of the stress system may
lead to osteoporosis and metabolic syndrome
...
Activation is
represented by solid green lines and inhibition by dashed red
lines
...
• Reported in 1943, issue of phytopathology by C
...
Ehrlich
...
He came up with this basic principle of toxicology:
The dose makes the poison
...
It is only the dose
which makes a thing poison
...
• Hormetic stress Resistance proteins- Protein Chaperons- HSP,
antioxidant enzymes, growth factors like – insulin-like growth
factor, brain derived neurotrophic factor
...
Mild Stress
No stress
Hormetic Response
Adaptive signaling
Autophagy
Unfolded protein response
Heatshock protein
Preconditioned state
Stress resistance
Cell survival
Intense stress
Cellular damage
Cell death
Hormesis governs the pleotropic pre-survival program
Dietary and Behavioral Neurohormesis
Dietary restriction
Physical exercise
BDNF- Brain derived neurotropic factor
GDNF-Glial cell line derived neurotropic factor
HSP- Heat shock protein
GRP- Glucose regulated protein
SSRI- Serotonin reuptake inhibitors
Neuroprotection
Neurogenesis
Synaptic Plasticity
Cognitive Enrichment
Cellular Stress Response
Serotonin
BDNF
GDNF
HSP-70
GRP-78
SSRI
Improved Glucose metabolism
Resistance to neurodegenerative disorders
Resistance to diabetic and cardiovascular disease
Mechanism of exercise, dietary restriction and cognitive stimulation
exert beneficial effects
Glutamate concentration
LOW
(Normal Synaptic activity)
Small / transient Calcium
influx
Maintenance of
function
MEDIUM
HIGH
(Cognitive Stimulation/
mild ischemia)
(Seizures, severe
ischemia)
Moderate/transient
calcium influx- stress
response
Large sustained/
calcium influx toxicity
Enhanced function and
disease resistance
Cell dysfunction, Cell
death
The excitatory amino acid neurotransmitter : a typical non-linear dose-response hormesis
mechanism
ROS,TNF,
Ischemia,
Aβ
Serine +
Palm Co A
SPT
Sphingomyelins
CERAMIDES
SMase
High
Mitochondrial
Alterations
ROS
CELL DEATH
Low
CAPP
TNF
HORMESIS
SPT- Serine Palmitoyl transferase
CAPP- Ceramide activated protein-phosphatase
A β - Amyloid beta peptide
Smase- Sphingomyelinase
TNF – Tumour necrosis factor
Ceramide, an endogenous stress-induced lipid that can induce hormesis or cell death