Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuroendocrinology > HPA Axis > Flashcards

HPA Axis Flashcards

1
Q

What is stress

A

Actual or anticipated disruption to homeostasis or well being (perturbation to homeostasis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Types of stress

A

Systemic/physical: (CV and metabolic) haemorrhage/visceral and somatic pain/ inflammation/malnutrition

Psychogenic/psychological: (social stress) isolation, hierarchy, unemployment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Stress activation in the brain stem

A

BS:
medullary and SC system - sympathetic NS
nucleus of solitary tract (NTS) - Limbic–>PVN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

central pathways regulating the stress response

A

inputs from higher centres: memory (medial septum/entorhinal cortex/cingulate cortex) & sensory processing (olfactory nuclei/piriform and insurlar cortex)
to… limbic processing: prefrontal cortex/hippocampus/amygdala

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how does stress affect the hippocampus

A

severe deficits in hippocampal dependent object recognition after multi-modal stress
structural neural remodelling (cortisol/glutamate/CRF/trophic factors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

connectomics

Maras PM et al., 2014

A

increase functional network connectivity between the hippocampus/amygdala/BNST and thalamus (gateway to the cortex) - cause restraint

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

experimental approaches

A
  • species (rodents) since primates more expensive
  • stress (majority acute psychogenic/restraint which is easy to observe/physical)
  • pharmacological/surgical manipulation
  • optogenetics - activate a specific neuronal population
  • DREADDS
  • fibre photometry
  • gradient-index (GRIN) lens imaging of neural activity via miniture fluorescent microscope
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what to measure when studying the HPA axis

A
  • ACTH/glucocorticoid
  • CRH/AVP in portal blood (hard to access in rodents then use sheep)
  • cfos (gene activation) - marks neuronal population activation
  • CRH/AVP/GR/MR glucocorticoid expression receptors
  • GRIN lens calcium imaging (observe neuronal firing)
  • in vivo studies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

HPA axis steps

A
  • stress
  • hypothalamus/PVN
    releases CRH/AVP
  • pituitary
    releases ACTH
  • adrenal cortex
    releases glucocorticoid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

PVN

A

located at the 3rd ventricle
parvocellular -dorsomedial/autonomic
increased c-fos mRNA during PVN activation in stress (timing is important)
CRH neurons labelled with dTomato –> in stress, there is an increase in c-fos
hypoglycaemic stress increases CRH mRNA in parvocellular PVN /restraint stress activates parvocellular neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

GCamP inserted into PVN CRH neurons (in-vivo calcium imaging)

Yuan et al., 2019

A

produces heatmap plot
sucrose = less stress response
shock increases the stress response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is glucocorticoid feedback

A

limits prolonged exposure to catabolic and other actions of GC
GC can cause neuropsychiatric pathologies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

glucocorticoid receptors

A

mineralocorticoid (MR) high affinity/basal activation
glucocorticoid (GR) low affinity/high levels needed for binding/activated during stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

MR/GR location

A

MR in limbic neurons (medial PFC)/amygdala/hippocampus
GR is ubiquitous (highly expressed in the PVN)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

responses to GC

A

genomic (delay) response - MR/GR TF, alters gene expression >30mins
non genomic (fast) response - membrane localised, mediated by secondary effectors (modulate ion channels, R,NT) 1-2 mins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

delayed feedback/rapid in the PVN

A

CRH/AVP have delayed response
rapid feedback: measure ACTH and cortisol - basal ACTH rise and decline as morning progresses (same in cortisol) = normal/provide prednisolone (GC) ACTH/cortisol decline = rapid pituitary response

17
Q

rapid response

A

iPVN dexamethasone (Dex) decreases stress response (restraint)
stress increases endocannabinoids in PVN
endocannabinoids initiate retrograde inhibition of glutamate:
CORT - CRHn R - release endocannabinoids - feedback to glutamatergic presynaptic neuron- switches OFF (silent -lost drive)

18
Q

CRH neurons in the PVN

A

CRF1 on GABA neurons - remove the CRF1 receptor - increase corticosterone

19
Q

24hrs of ACTH and cortisol

A

portable microdialysis pump attached to microdialysis catheter
pulsatile GC release (critical for normal functioning)
occurs in circadian rhythm and disease states

20
Q

what is the effect of proteasomes

A

removes GR only = pulsatile GR translocation
gene pulsing occurs

21
Q

functions of glucocorticoids

A

metabolism
regulates innate and acquired immunity
cell growth/differentiation
CV function
provide energy
bone turnover

22
Q

role of pulsatile cortisol

A

improves cognition and sleep

23
Q

Hypercortisolism (consequences of oversecretion of GCs)

A

cushing syndrome
hypertension
steroid diabetes
muscle wasting
immunosuppression

24
Q

peripheral pulse oscillator

A

continuous CRF signal induces pulses
continuous CRH stimulates ACTH and CORT therefore pulsatile CRH not needed, lag between ACTH/CORT
pulsatile is the most efficient method of neuropeptide release
cluster action potentials = more release

25
Q

pulses of ACTH and CORT

A

feedforward = ACTH stimulates CORT synthesis from the adrenal cortex
feedback = CORT fast inhibit of ACTH release
both are the role of a peripheral oscillator

26
Q

CRH (executive organiser)

A

41aa - humans and rats have identical peptides, differ by 7 aa
CRH and CRH-R associated with stress response (hippocampus and amygdala)
family of ligands which bind to CRH-R: Urocortin 1 (Ucn1)/UcnII/UcnIII

27
Q

CRH system

A

in the cortex/cerebellum: amygdala/BSTN/hippocampus (activate fight or flight)
CRH receptors:
CRH-R1 (pituitary-ACTH)
CRH-R2:
R2a - septum/hypothalamus/raphe/NTS
R2B - glia/endothelial/amygdala
R2y - (not in rodents) - septum/amygdala/hippocampus/frontal cortex

28
Q

CRH receptor binding

A

preference for CRH-R1 (less to R2)
UcnI - R1/R2
UcnII/III - R2 selective
R1 = anxiogenic
R2 = anxiogenic and anxiolytic
CRH-BP = influences amount of peptide available

29
Q

CRH antagonists

A

a-helical CRH1-41
CRH-R1 antagonist is antalarmin

30
Q

genetic manipulation of CRH system

A

conditional KO of CRH R/overexpress CRH
stress increases ACTH
CRH-R1 KO in stress: no effect

31
Q

conditional limbic CRH-R1 KO/CRH-R2 KO

A

at d20 - reduce ACTH feedback, CaMKII expressed (allows development of neuronal circuitries)
R2 KO - increases anxious behaviour (compared to R1 KO)
R2 ligand = stresscopin (enhances the behavioral response)
Limbic CRH-R1 required for central control of HPA system feedback (functions independenly of HPA axis so does not affect cortisol levels)

32
Q

DREADD inhibition of UcnIII in the medial amygdala/optogenetic activation of UcnIII terminals in the PVN nucleus

Ivanova et al., 2021

A

blocks predator odour (TMT) stress-induced CORT rise in female mice
ChR2 increases CORT release in female mice

33
Q

dysregulation of the CRH system

A

chronically elevated CRH implicated in human stress related/affective disorders/anxiety/major depression

34
Q

potential depression treatment

A

CRH-R1 antagonist NBI 30775/R121919 improves depression

Neuroendocrinology (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions