L21

Question 1

How do environmental factors perturbing animal homeostasis effect development?

Answer 1

Through epigenetic mechanisms

Long term effects depend on type and severity of exposure, timing of exposure, sex and effects on germ cells

Question 2

When are males and females most susceptible to environmental factors?

Answer 2

M-prenatal, F-postnatal

Question 3

Relevance of the postnatal and pubertal periods?

Answer 3

Windows of susceptibility, depend on: peak and decline in synapses, neuromodulators, neurotrophins, cerebral blood flow + metabolism, rise in gonadal hormones

Question 4

What is epigenetic modification?

Answer 4

Functionally relevant chromatin modifications that alter gene expression but not DNA sequence

Question 5

Types of epigenetic modification?

Answer 5

DNA methylation, histone modification, ncRNAs

Question 6

DNA methylation

Answer 6

Cytosine converted to 5 methyl cytosine by DNMTs (SAM+CH3->SAMH); creates CpG islands, which are transcription silencing

Question 7

Histone modification

Answer 7

Acetylation (big role in transcription regulation): HATs transfer acetyl groups to lysine residues (activating chromatin); HDACs remove acetyl groups (silencing)
Methylation: HMTs transfer methyl groups to lysine/arginine residues of substrate proteins, associated with repressing chromatin
Phosphorylation: limited to cell cycle mediated changes in chromatin; role in DNA damage response
(Ubiquitylation/ubiquitination, ADP ribosylation)

Question 8

ncRNAs

Answer 8

70% of RNA
lncRNAs- chromatin modifications, Pol II regulation, transcriptional interference
miRNAs AND lncRNAs- splicing, editing, mRNA stability, translation initiation

Question 9

Epigenetic …

Answer 9

… repressive chromatin show high levels of DNA methylation, repressive histone marks [OFF]; permissive chromatin show low levels of DNA methylation, active histone marks [ON]
Early environmental stimuli (stress)-> NTs/Rs -> 2nd messengers -> TFs + epigenetic regulators expressed -> long lasting adaptive changes on neuronal function -> future susceptibility to illness

Question 10

Prenatal stress:

Answer 10

Physiological/psychological, mediated by MAs, neuropeptides, steroids, involves brain stem, Hyp, Am, PFC, HPC
Depends on age, sex, background, environment, experience and timing
Can be acute or chronic