L11 - Stress Axis

Question 1

What do the nuceli involved in the stress axis respond to

What do they give rise to

Answer 1

Progenitors transiently expressed Shh or respond to Shh (From FGF10+ Shh prog) theese give rise to ARC and VMN - includes the pomc+ ARC neurones and sf1+ VMN neurones

Progenitors repressed by Shh will give rise to PVN neurones - includes CRH+ neurones

Question 2

What is needed when researching behaviour

Answer 2

Very high n numbers

Question 3

What neurones are important for the release of corticotrophin releasing factor?

Answer 3

Corticotrophin-releasing hormone neurones
Pomc neurones
Steroidogenic factor neurones

Question 4

What is steroidogenic factor required for

Answer 4

Important for the development of the steroidogenic factor neurones

Question 5

What is the major stress hormone

Where is it released from

Answer 5

Cortisol

Major adrenal gland

Question 6

Pomc neurones release ….

Answer 6

Pre currsor protein to ACTH

Question 7

What is ACTH why is it important

Answer 7

Causes the release of cortisol from the adrenal gland

Question 8

Control of cortisol release by what levels

Answer 8

Control of cortisol release from adrenal controlled by ACTH from the pituitary

BUT is all controlled by the three types of neurones in the hypothalamus

Question 9

What gene can be seen to be deleted in schizophrenia

Answer 9

DISC1

This is a high risk factor

Question 10

How was the deletion of DISC1 identified?

Answer 10

Through genetic analysis of an inbred family with a high risk of mental problems

Each of the individuals with illness had a mutated for of DISC1

Question 11

what is the first question when looking at DISC1

Answer 11

WHERE IS THE GENE EXPRESSED

Question 12

Where is DISC1 expressed in the zbrafish embryo

Answer 12

Disc1 mRNA and protein are expressed in the developing hypothalamus

Question 13

How was disc1 mRNA expression localisation visualised?

Answer 13

Using in-situ hybridisation

Question 14

Describe disc1 expression in relation to other genes expressed in thee hypothalamus

Answer 14

Overlaps with cells that are FGF or Shh+

Not expressed in other regions of the brain - specific to the hypothaalmus

Question 15

Describe how mutants of the disc1 gene was created

Answer 15

2 points mutations at L115 and Y472

No full length mRNA or protein

Question 16

Describe the strucutre of disc1 protein

Answer 16

Globular domain at the N terminus

A helix at the C terminus

Question 17

What is implicit of the a heliz at the c terminus of disc1

Answer 17

Potential for coiled coils - suggests there may be interactions with other proteins

Question 18

What is the second question researchers asked about DISC1

Answer 18

What is the effect on the hypothalamus - morphology and gene expression

Question 19

Describe what is seen in the hypothalamus of DISC1 mutant

Answer 19

Premature differention - not enough progenitors made
Less mRNA of progenitor marker in the mutant

INTERFERENCE WITH PROGENITOR (RUNNING OUT OF STEM/PROGENITOR CELLS)

Question 20

Describe the effect of mutant disc1 on the following

Pomc+ ARC neurones

Sf1+ VMN neurones

Crh+ PVN neurones

Answer 20

Pomc+ ARC neurones
Reduced

Sf1+ VMN neurones
Increased

Crh+ PVN neurones
Increased

Question 21

DISC1 mutations leads to ______________ of hypothalamic neurones involved in _______________

Answer 21

abberant development

Stress regultion

Question 22

How do we see if difference in neurones confers a behavioural output?

Answer 22

Behavoiural assays for stress

Neuroendicrine function

Question 23

How is neuroendocrine levels changed in the disc1 mutant

Answer 23

Upregulation of neurohormones after stress

Upregulation of cortisol after stress

Question 24

How to stress a ZF (2)

Answer 24

ZF from ganges (non salty)
Stress with salt water 0 move away from the high salt

If ZF damaged and skin is cut release substance other fish respond to with heightened stress

Question 25

What is the substance released by ZF when cut called

Answer 25

Shreckstoff

Question 26

What is the effect of DISC1 mutatns on the stress resposnse

Answer 26

If stress a sifh with the DISC1 mutant it CANT RESPOND TO STRESS

Question 27

What is the effect of stress on cortisol levels in the DISC1 mutant

Answer 27

Levels of cortisol in the DISC1 mutants dont increase

Question 28

Is stress important

Answer 28

Yes we need to be able to be stressed and to be able to repsond to it

Question 29

What is the effect of cortisol on the stress axis after the stressful situation has occured

Answer 29

Cortisol downregulates the entire pathway

Question 30

What sorts of stress are required to aid dev

Answer 30

Oscillations to tune to being in a steady state where you dont want to deviate too far from the set point - WAVE IS GOOD - helps to understand where the rest (median) is