The HPA Axis

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Broad description of stress
Actual or anticipated disruption of homeostasis or an anticipated threat to wellbeing.
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Two types of adaptive/allosteric responses to stress
Initial - stressor specific. Long term - non-specific, maladaptive allostatic load.
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Two systems that stress activates
Neuroendocrine (HPA Axis) and Autonomic - Sympathetic/parasym
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Where is the HPA axis?
between the hypothalamus and the anterior pituitary, via the median eminence.
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What is released from the ant pit following stress
corticotroph cells release ACTH
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what does ACTH go on to do?
stimulate the release of cortisol from the adrenal cortex
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two natures/types of stress?
Systemic/physical stress. and Psychogenic/psychological stress
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What is the neurochemical signature of systemic/physical stress
major homeostatic perturbations
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What is the neurochemical signature of psychogenic/psychologicla stress
incorporation of learning, emotional responses, fear, anxiety.
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what kind of challenges are percieved by overlapping brain circuits. in the brain stem
environmental and homeostatic challenges. ?
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What does the limbic system integrate
psychogenic stress signals - cognitive, emotional, visceral responses.
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What experimental approaches to studying the HPA responses to stress?
Rodents put under acute psychogenic or physical stress, particualr emphasis on chronic variable mild stress. Or pharmacological or surgical manipulations to target specific pathways
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What end points are looked at in stressed animal models
plasma ACTH and cortiocosterone. AVP/CRH in portal blood. Hypothalamic CRH and AVP mRNA and protien. gene activation in the brain, receptor expression
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Describe the hormones in the HPA axis -
PVN releases CRH, AVP. the ant pit releases ACTH, the adrenal releases glucocorticoids.
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three subsections of the PVN
A) dorsomedial parvocellular, b) dorsolateral magnocellular, c) autonomic parvocelular.
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What does the Dorsomedial parvocellular release
CRH/AVP. TRH, SRIF, DA
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How does the PVN activate during stress?
Increased cfos mRNA expression 30 mins following stress, particuarly in CRH neurons in the PVN
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What does this mean?
Stress leads to CRH release from the PVN
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How does acute restraint stresss affect AVP mRNA
AVP release from the parvocellular subdivision of the PVN
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What effect do glucocorticoids have on the pit and hypothalamus
Inhibitory feedback
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What do GCs bind to?
Mineralcorticoid receptors, glucocorticoid receptors.
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What happens following binding?
Activation of GR and MR ligand driven TFs to regulate the expression of specific genes
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Where are these receptors expressed
MR - limbic neurons. GR- highest in the PVN
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Differences in affinity/role
MRs have high affinity, so maintain basal activation. GRs have lower affinity, so are activated during stress in a reactive role.
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How long do the genomic effects of glu feedback take to appear
30 mins.
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How long do the non-genomic effects take to appear
1-2 mins
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A rapid effect of cort signalling
Initiating the synthesis of Cannabinoids
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What do cannabinoids then do?
act on presynaptic CB1 receptors and switch off glutamate signalling
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What happens when you disrupt GR in the PVN
There is an increase in HPA axis activity in basal conditions. Demonstrating loss of negative feedback under basal conditions.
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How does ATCH/cortisol change in the CR
ramps up in the early hours of the morning, decreases in late afternoon/evening.
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Why is glucocorticoid released in pulses
much greater control. prevents receptor desensitisation. Disease states reflect loss of pulsivity. Enables 'gene pulsing'
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What is meant by gene pulsing
Cells rapidly detect and respond to changes to circulating glucocorticod levels. prevents the system from losing responsivity.
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How does the HPA response change depending on CR
bigger response on the rise, rather than the fall
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How is Cort released in a pulsatile way?
From continous administration of CRH.
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Card 2

Front

Two types of adaptive/allosteric responses to stress

Back

Initial - stressor specific. Long term - non-specific, maladaptive allostatic load.

Card 3

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Two systems that stress activates

Back

Preview of the front of card 3

Card 4

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Where is the HPA axis?

Back

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Card 5

Front

What is released from the ant pit following stress

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