Stress 2 Flashcards
What are the two kinds of receptors in the limbic system involved in cortisol feedback?
MR and GR
How do the receptors changed gene transcription. Name two ways.
- directly binding to recognition sites in the DNA
2. indirectly via interactions with other transcription factors
What effect does excess cortisol have on the hippocampus?
It will down regulate various cell signals including action of BDNF on synaptic integrity. A treaty for this problem will enhance BDNF and monoamine neuromodulation.
MR - high or low affinity for cortisol?
High!
Do MRs increase decrease of maintain excitability of the hippocampal neurons?
maintain
GR - high or low affinity for cortisol?
low
GR are only when?
with high levels of stress-related cortisol
As cortisol levels increase at later stages of stress, GR activity leads to inhibition or activation of stress response?
Inhibtion
MR - fast or slow response
fast
GR - fast or slow response
slow
What are the three phases of brain stress responses?
Stress, recovery, and adaptation
stress generates responses from where?
the limbic system
After a stress response is generate from the limbic system, where are they projected to?
The OVN in the hypothalamus and the HPA axis
After a stressor, when do cortisol levels peak?
30-45 minutes
In the Stress phase, increased cortisol levels bind to which type of receptors?
MR
The binding of cortisol to MRs has what response in the body?
Enhanced arousal, vigilance, alertness, and attention. (non-genomic action through MRs)
When do the recovery and adaption stages occur?
After 1-2 hours
In the recovery and adaption stages, cortisol decreases but there is still enough to suppress the stress response from the initial phase via which type of receptors? Is it a genomic or nongenomic response?
GR - genomic
What else occurs in the recovery and adaptation phases besides suppression?
consolidation and preservation of info about the stressful event. (Memory!!)
Cortisol facilitated memory and learning is dependent on what brain structure? What else is required for proper learning?
Hippocampus. - TIMING!
Stress within the context of learning release what three things? What do they facilitate with?
NA, CRH, and CORT - all of which facilitate the ongoing precesses of perception and attention in the initial phases of learning
cortisol also initiated a ________ pathways which facilitates consolidation of relevant info and temporarily ______ input of unrelated info.
gene-mediated; inhibits
If stress precede learning, when will the gene-mediates suppression of activity occur?
During the time when you want to learn the new task!
Cortisol feedback on the AMYGDALA: the amygdala stimulates or inhibits the HPA axis during stress?
stimulates
cortisol feedback increases or decreases amygdala’s responses to stress by facilitating its activation by ____(what neurotransmitter?)
increases; NE
NOTE how both _____ and _____ enhance amygdala activity in response to stress.
NE and cortisol…the two limbs of the stress response
Cortisol feedback on the PFC: in acute stress does cortisol activate or inhibits MPFC?
activates
What does activation of the mPFC do in acute stress? 2 things.
improves working memory and helps terminate HPA stress response
During Greater stress, high levels or cortisol do what to working memory?
disrupt it and cause distractibility!
In Chronic Stress are the glucocorticoid receptors down regulated or up regulated in the mPFC?
downregulated
What does down regulation of the glucocorticoid receptors in the mPFC during chronic stress or aging associated with?
impaired negative feedback regulation by cortisol AKA hypercortisolism
Excess cortisol can lead to a reduction or increase in top-down regulation of the amygdala?
reduction
Chronic stress leads to increased cortisol release because of up regulation of what two things?
VP and ACTH receptors
How does up regulated VP lead to cortisol resistance?
VP is ledd inhibited by cortisol feedback compared to CRH leading to increased cortisol release
What in the clinical presentation of someone with Melancholic depression?
insomnia, anorexia, motor agitation, over arousal
What is the cause of melancholic depression?
HPA-axis hyperactivity and hypercortisolemia (higher CRH levels)
What other conditions might someone with atypical drepression have?
Inflammatory and metabolic dysregulation: higher levels on inflammatory markers, BMI, waist circumference, and triglycerides. Lower HDL cholesterol.
How would a patent with atypical depression present in the clinic?
hypersomnia, weight gain, lethargy,
What do cortisol levels look like in a patient with atypical depression?
NORMAL!
What is the switch hypothesis?
As stesors becomes increased or sustained, CRH secretion decreases in the PVN, while AVP secretion increases.
In CRH associate with chronic or acute stressors?
acute
Is AVP associate with acute or chronic stessors?
chronic
Brain exposure to what two things leads to experience of melancholic depression?
CRH and cortisol
Brain exposure to what what results in symptoms seen in atypical depression?
Cortisol alone, or cortisol +AVP
What happens to the circadian fluctuations of cortisol during chronic stress?
They are flattened
Chronic stress with increase or reduce the CRH sensitivity to stressors?
reduce
What will a flattened circadian flu cation in cortisol do to someones sleep?
Cause sleep disruption which will elevate evening cortisol and glucose levels…this could lead to insulin resistance
Throughout the day, when does cortisol secretion peak?
About an hour or so after waking
Throughout the day, when are cortisol levels at their minimum?
In the evening
With chronic stress, what changes to the amount of cortisol secretion in the morning and in the evening?
lowers cortisol in the morning, increases cortisol in the evening
What are the pulsatile secretions in the circadian flu cations necessary for?
Prevention of receptor desensitization. And it may also represent periods of enhances stress responsiveness.
How does fasting effect cortisol levels?
enchances them
How does fasting change cortisol secretions?
It delays maximal blood cortisol concentrations to the early afternoon
What metabolic effects results from hypercortisolism?
Osteoporosis
Insulin resistence
vascular disease
What affect does hypercortisolism have on the amygdala?
Can cause amygdala hypertrophy and hyperactivity -> increased emotion responsiveness
What effect does hypercortisolism have on the PFCand hippocampus?
Reduction in synaptic contact and volume - disfunction in cognition, working memory, and memory consolidation
How can the negative effect of hypercortisolism be revered in the hippocampus and PFC?
With lithium and antidepressants
Why are woman twice as likely to develop major depressive disorder?
Estrogen is associated with greater stress-related dendritic remodeling in the nPFC
How would an early life trauma effect your current stress levels?
They increase the number and sensitivity of CRH neurons
What does early trauma do to epigenetics?
It causes epigenetic suppression of BDNF, a factor that is necessary to limit neural degeneration in hippocampus relate to stress
In the absence of stress is the BDNF gene coiled or uncoiled?
coiled
In chronic stress, does the demethylation of the BDNF gene open or close the gene?
close
Does stress result in inhibition or release of pro-inflammatory cytokines?
release!
How to cytokines disrupt the feedback control of cortisol?
They diminish central cortisol receptor sensitivity
Inflammatory cytokine interfere with neuromodulation. specifically what neurotransmitters?
Dopamine (DA), Sertonin (5HT), and Norepinephrin (NE)
In depression, disruption of seratonin, dopa, and NE transmission impairs what?
the regulatory feedback loops that turn of the stress response
What causes neuropinflammation?
Classical factors: infection, autoimmunity, toxins
Factors that lead to enhanced neuronal activity :noxious stimuli, psychological stress and epileptic seizures
In learning: circadian glucocorticoid peaks promote what?
Postsynaptic dendritic spine formation
In learning: circadian glucocorticoid troughs promote what?
stabilization of newly formed spines that are important for long-term memory retention
chronic and excessive exposure to stress eliminates what necessary steps to learning?
- learning associated new
2. it also disrupts acquired memories
What causes Hypoadrenalism? (Addison’s disease)
Atrophy of tissue due to autoimmune, TB, or cancer
What happen to cortisol levels in Addison’s disease?
decrease
What are the symptoms of Addison’s disease?
Hypoglycemia between meals
Decreased gluconeogensis
Susceptible to Stress
Blotchy melanin pigmentation of mucous membrane and skin
Aldosterone decrease leads to excess excretion of sodium and water and excess reabsorption of potassium.
What is Hyperadenalism calles?
Cushing’s syndrome
What is Cushing’s syndrome caused by?
Excess cortisol due to any etiology
Hypersecretion of ACTH from a pituitary adenoma
Autoimmune hyperplasia of adrenal cortical cells
What are the symptoms of Chushing’s syndrome?
Buffalo Torso Hyperglycemia (Insulin resistance) Protein loss Aldosterone excess: facial edema, hypertension, hypokalemia DHEA excess, acne, hirsutism
