The Stress Axis Flashcards
Tuberal progenitors give rise to…
tuberal neurons in the Arc nucleus (pomc+ and NPY)
Where are corticotropin-releasing hormones located?
the paraventricular nucleus
their axons project into the median emminence
What is the stress axis regulated by?
Corticotropin-releasing hormone neurons
Where is Crh released into?
portal capillary network
it then travels to the anterior pituitary (directly beneath the median eminence
Steps of the stress axis:
- Crh is released into the portal capillary network and travels to the anterior pituitary
- Crh bind to corticotrophs in the anterior pituitary
- Corticotrophs release Adrenocorticotropic hormone (ACTH) - enters the circulatory system
- ACTH stimulates the adrenal gland to secrete cortisol
How does the body make the stress resonse acute?
Cortisol binds to the mineralocorticoid receptor and the glucocorticoid receptor in cells of the pituitary
- dampens response (inhibits)
What is DISC1?
Disrupted in schizophrenia
genetric risk factor for mental illness
- major translocation in the DISC1 gene
What is DISC1 important for in zebrafish?
DISC1 is expressed in the developing hypothalamus
in cells deciding whether to become tuberal or mammillary/paraventricular
- affects WNT signalling (important in this decision)
What were the changes seen in DISC1 mutant zebrafish?
fewer hypothalamic progenitors
fewer pomc ARC neurons
more crh+ PVN neurons
What is used to induce stress in fish?
NaCl and Shreckstoff (chemical released by hurt fish)
Stress induction in WT vs DISC1 mutant fish?
WT: results in rapid swimming behaviour
DISC1 mutant: no response
cortisol is not upregulated in the DISC1 mutant
What does the lack of stress response in DISC1 mutants suggest?
mental health disorders are manifested through an inability to achieve a normal homeostatic response
