The Stress Axis

Question 1

What is found within the PVN nucleus?

Answer 1

Corticotrphin releasing hormone neurons (CTR+ neurons)

Question 2

Where do PVN neurons project?

Answer 2

Project axons to median eminence and posterior pituitary

Question 3

What do the PVN neurons release?

Answer 3

• neurohormones into portal capillary network
• Regulates hormone release from endocrine cells in anterior pituitary (corticotrophs)

Question 4

What is the major stress hormone?

Answer 4

• cortisol
• released from adrenal gland

Question 5

How is cortisol regulated?

Answer 5

Cortisol regulation follows the HPA axis:

1. Hypothalamus releases CRH (corticotropin-releasing hormone) in response to stress or circadian signals.
2. CRH stimulates the anterior pituitary to release ACTH (adrenocorticotropic hormone).
3. ACTH signals the adrenal cortex to secrete cortisol.
4. Cortisol provides negative feedback to the hypothalamus and pituitary to suppress further CRH and ACTH release, maintaining balance.

Question 6

What other neurons feed in to regulate this pathway?

Answer 6

POMC
Third class of neurons called: steroidogenic factor 1 (SF1)

Question 7

What does DISC1 stand for?

Answer 7

Disrupted in Schizophrenia

Question 8

What is DISC1?

Answer 8

A gene which serves as a genetic risk factor for mental illness when mutated
- Found through genetic analysis of an inbred family with a high risk of mental problems

Question 9

Where is DISC1 expressed in the brain?

Answer 9

(zebrafish)
- mRNA encoding DISC1 and DISC1 protein are expressed exclusively in the hypothalamus
- DISC1 is expressed in cells that are becoming progenitors (similar to HypFP)

Question 10

From knowing where DISC1 is expressed what was the next step?

Answer 10

Two transgenic lines of fish with 2 point mutants
Neither mutants made no full length mRNA or protein

Question 11

What happens in Disc1 mutants?

Answer 11

In Disc1 mutants, the tuberal hypothalamus progenitors are absent. This is evidenced by the lack of the progenitor marker Rax, indicating a disruption in the development of tuberal hypothalamus progenitors.

Question 12

How do you measure a stress response?

Answer 12

1. Behavioural assay
2. Neuroendocrine function

Question 13

How have zebrafish been used to do stress behavioural assays?

Answer 13

• When fish get attacked they release a pheromone triggered by scratched skin
• WT fish when presented with this ‘Schrekstoff’ displayed lots of erratic behaviour then freezes
• Disc1 mutant fish after exposure is oblivious, no erratic movement or freezing

Question 14

How else can you measure stress?

Answer 14

• Expose fish to stress, kill it and look at cortisol
• WT always show increase in circulating cortisol in response to Shrekstoff
• Disc1 mutant have a blunted stress response