Lecture about paper: Epigenetic programming by maternal behavior Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

There are natural variations amongst maternal care of rats. What variations are there?

A

High and low licking and grooming (and arched back nursing)

Note: from now on licking and grooming is LG.

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

Fill in:

A normal stress system has a high or low sensitivity for negative feedback.

A

A normal stress system has a high sensitivity for negative feedback.

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

Explain the genetic pathway that occurs in a baby mouse that has high LG.

A

High LG results in a healthy stress system where:

  • Serotonin (5-HT) is produced that binds to its receptor (5-HT7).
  • downstreams cAMP is activated, which activates PKA.
  • PKA phosphorylates effector proteins/activators (e.g. CBP) of transcription factors
  • CBP binds and activates the transcription factor NFGIA
  • NGFIA is able to bind to the noncoding Ipromotor
  • transcription of GR (glucocorticoid receptor)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the result of the increased expression of GR as a consequence of high LG?

A

Low corticosterone levels, low anxiety, high licking or grooming.

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

Explain the genetic pathway that occurs in a baby mouse that has low LG.

A

In baby mice with low LG, the noncoding Ipromotor is methylated. This prevents that the transcription factor NGFIA can bind to this promotor and this prevents/reduces the expression of GR.

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

What is the result of the decreased expression of GR as a consequence of low LG?

A

High corticosterone levels, high anxiety, low licking and grooming

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

What is parental or epigenetic imprinting?

A

Epigenetic changes that are already present in the DNA of the cell’s organism. This causes genes to be expressed in a parent-of-origin-specific manner.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Exon Ihas several areas that can be methylated. But when is methylation only possible?

A

Methylation is only possible when cytosine is followed by guanine (CpG island)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Two regions of the Iexon are of interest in this article. The 5’ (site 16) and 3’ (site 17) end of the CpG island, seen in the picture. Are there differences in methylation in rats with low or high LG?

A

Yes, it is seen that the 5’ end or region/site 16 is highly methylated in rats with low LG and almost not methylated in rats with high LG.

3’ end or region/site 17 is methylated in both high and low LG rats. This would mean that methylation of this region, doesn’t interfere with binding of the transcription factor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is seen here?

A

Methylation is also seen in other (15) CpG regions of the Iexon, for high and low LG rats. But methylation is highest for the low LG rats.

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

Why can’t you just conclude based on the fact that you see differences in methylation in the Iexon, that this is the cause of differences in stress levels of rats?

A

Beause in between epigenetic changes and behavior, are more steps, like mRNA, proteins etc.

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

What is done in this study to confirm (or deny) that epigenetic changes are the cause of changes in stress level and are caused by the behavior of the mother?

A

Cross fostering, where the litter from high LG mothers are placed with low LG mothers. If the methylation is dependent on the behavior of the mother, you would expect that the situation created by a low LG mother is restored by the high LG mother.

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

Can the conclusion of this study be based on solely cross fostering of litter from high LG mother placed with low LG mother?

A

No, you need to check for causality because high LG mother rats might not recognize adopted litter, so you need a control where the litter of high LG mother is placed with another high LG mother.

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

What can you conclude based on this picture, where the effect of cross fostering on methylation patterns is measured?

A

Based on the graph of region 16/5’ CpG, you can state that methylation is dependent on the mothers behavior.

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

What’s seen in this picture where they measure methylation patterns during embryonic and pup development?

Note: no cross-fostering is performed here

A
  • E20 = embryonic day 20, P1 = first dat of life out of the womb, P90 = adult
  • The region 17/3’CpG is not interesting, region 16/5’CpG is interesting.
  • You see that in region 16, there’s no methylation during pregancy (E20). Once they’re born (P1) all of the rats have methylation and on P6 there’s a difference between the two groups of high and low LG pups → probably due to the mother’s behavior.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is de novo methylation?

A

Automatic methylation immediately after birth

17
Q

What’s the next step after cross fostering and measuring methylation levels during and after birth?

A

Investigating whether the level of methylation have an affect on protein level and whether this has an effect on hormone (cortisol) levels.

18
Q

What’s seen in regard to protein density when you compare low and high LG pups?

A

That the GR protein density from rats raised by low LG mother is way less compared to rats raised by high LG mothers.

19
Q

Can you conclude based on this picture that epigenetic modifications influence protein density?

A

No, because there are more ways to influence protein density besides epigenetic modification.

20
Q

What’s used to study whether epigenetic modifications do influence protein density (and to confirm for causality)?

A

Demethylating everything by TSA (note that TSA is administered to rats via a certain tube on the brains while they’re alive → gives stress, so therefore a control (vehicle) is also used.

21
Q

What’s seen in regard to protein density when TSA is used to delete (as much as possible) methylation?

A

That removing methylation does influence protein density. The vehicle/control still has lower levels of protein density (probably due to methylation), while the the removal of methylation by TSA increases protein density in both groups.

22
Q

So we just confirmed that protein density is affected by methylation (by comparing it with protein density where TSA was used to remove methylation). What is the last step in this study?

A

To measure hormone concentration during stress

23
Q

What is expected in rats raised by low or high LG when stress is induced by putting them in a small plastic box where movement is restricted?

A
  • In rats with high LG in vehicle and TSA, it’s expected that they have a healthy stress system. So stress should go down, when the plastic box is removed.
  • In rats with low LG in vehicle and TSA, it’s expected that they don’t have a good stress system. So stress is expected to stay high, even when the box is removed.
24
Q

What is seen in rats raised by low or high LG when stress is induced by putting them in a small plastic box where movement is restricted?

A

See picture

25
Q

What explanation is there for low LG rats that exhibit high stress levels even after the stressful event has gone away?

A

Low LG rats have more methylation → less protein (GR) → less molecules for sensitive negative feedback system → higher and longer stress

(Baseline of stress of low LG rats is as high as the peak stress of high LG rats → almost twice as high)

26
Q

What is the expectation if the methylation is removed in low LG rats and the same stress experiment is performed?

A

The expectation is that the amounts of GR will increase and that the stress system will work the same as in high LG rats. This is the case, low LG rats have a normal stress sytem when methylation is erased.