Stress Flashcards
HPA axis
Neuroendocrine output, slower response so prolongs initial stress response from sympatho-adrenal-medullary axis.
PVN activated which releases CRH, which causes ACTH release from the pituitary, which acts on the adrenal gland causing it to release GCs (corticosterone in rodents, cortisol in humans).
Circulating GC bind to GCRs in hypothalamus which affects release of CRH = negative feedback loop.
Higher expression of GCRs potentiates GC feedback (more sensitive) so lowered stress response. Axis switched off more effectively.
Damaging effects of GCs
Prevent neurogenesis in HC so impaired learning and memory.
Decreases synaptic plasticity.
Liu 2000
Rats of high-LG-ABN mothers performed better on Morris water maze.
= better spatial learning & memory.
Increased NMDAR & BDNF expression & cholinergic innervation of HC.
Offspring of low-LG mothers cross-fostered to high-LG mothers = low stress responses. Increased tactile stimulation leads to more NDMAR / BDNF expression so synapse proliferation etc, enhances HC growth.
But cross-fostered pups from high-LG to low-LG still had lowered stress response so have higher expression of NMDAR etc anyway? Genetic or in utero factors from high-LG mother can provide protection.
Francis 1999
If pups handled = mothers lick more.
Experimentally-induced high-LG behaviour in low-LG mothers = lowered stress responses in offspring, who then passed this on to their offspring.
Zhang 2013
Low-LG mothers had low levels of histone modifications in actively transcribed regions of GCR gene.
Also have high DNA methylation.
Epigenetic mechanism underlying stress response
High-LG mothers = higher HC 5HTR expression.
5HT elicits intracellular signalling cascade, producing NGFIA (transcription factor).
NGFIA helps encode Nr3c1 (decreases DNA methylation) which activates expression of GCRs.
Tactile stimulation from good mothering upregulates 5HTRs in offspring. So more NGFIA produced so less DNA methylation & more histone modifications = more Nr3c1 encoded so more GCRs expressed, and lower anxiety levels.
McGowan 2009
Suicide victims who were also abused in childhood = lower HC GCRs & Nr3c1 had higher methylation levels
Bader 2014
Children of Holocaust survivors had lower cortisol levels & increased sensitivity to stress if mother had PTSD, and if mother was older at time of exposure.
Yehuda 2005
1 year old babies of mothers who had PTSD post-9/11 had sig lower urinary cortisol than babies of mothers without PTSD after 9/11.
Suggests in utero factors or early life experiences crucial in shaping stress responses & risk of PTSD in later life.
Lernher 2014
Children of mothers with PTSD had higher GC sensitivity.
Suggests link between epigenetic mechanisms intertransgenerational GC programming.
Hettema 2001
Twin studies suggest 30-40% variation in anxiety levels between individuals can be explained by genetic factors.
Caspi 2002
Polymorphisms in MAOA (breaks down 5HT, NA, DA) promotor.
Maltreated boys with low MAOA activity = higher risk of antisocial behaviour as adults.
But not in boys with high MAOA activity so must confer some protection against adverse early life experiences.
Caspi 2003
Childhood abuse & no. of stressful early life events associated with risk of depression only in those with s/s or l/s alleles for 5HTT gene, not l/l.
Gross & Hen 2004
Twin studies found low HC vol = more susceptible to PSTD (sig inverse correlation).
Chronic stress from trauma leads to increased HPA activation so more GC released = HC damage?
No! Predisposing factor instead. Not effect of disease.
Liu 1997
Offspring of high-LG mothers = lower plasma corticosterone & ACTH in response to restraint stress.
Lower CRH mRNA in PVN, but
increased GCR mRNA expression.
