the stressed brain

Question 1

list the aspects of the limbic system and briefly describe their functions

Answer 1

hippocampus:

• learning from experience
• determines if a threat
• communicates heavily with hypothalamus —> hormonal response

olfactory bulb:
- direct input into brain (bypasses thalamus)

cingulate cortex:

• perception of pain / degree of pain
• visceral

stria terminalis:

• communicating aromas and smells
• affecting amygdala and hippocampus

prefrontal cortex:
- logic and reasoning

Question 2

what can occur if the amygdala is removed?

Answer 2

• sexual behaviour lost
• facial emotional recognition lost
• appetite lost

Question 3

what are the effects of SNS activation?

draw a diagram

Answer 3

stressor perceived in hypothalamus

1)
• hypothalamus activates SNS (very fast)
• activates adrenal medulla –> adrenaline release
• adrenaline stimulates glucagon release and inhibits insulin release in endocrine pancreas
• adrenaline causes vasoconstriction in smooth muscle –> decreased blood flow in kidneys –> increase renin, angiotensin, aldosterone

2)
• hypothalamus causes increase in CRH which acts on ant. pituitary
• ant. pituitary stimulates ACTH –> acts on adrenal cortex to increase cortisol
• causes breakdown of glucose and production of ATP

3)
• hypothalamus stimulates posterior pituitary
• releases vasopressin –> effects blood pressure/flow

Question 4

describe how stress can impact memory

Answer 4

• threat = release of adrenaline from adrenal medulla, persistent threat = release of cortisol
• cortisol remains in the brain much longer than adrenaline, therefore continues to impact brain cells
• cortisol diverts blood supply to muscles
• diminished blood flow to brain, therefore less glucose i.e. energy supply
• energy crisis in hippocampus —> compromised ability to create new memories

Question 5

describe how over-excitation of neurons can lead to disease

Answer 5

• excitation requires ATP ∴ over-excited neurons do not have enough ATP to sustain normal function
• due to the ATP deficit, brain begins using oxygen to create ATP
• more oxygen in brain = higher chance of free-radical formation
• immune system is compromised due to stress ∴ if a free radical hits DNA, mutations will be free to replicate
• —-> cancer in somatic cells
• —-> CVD in blood vessels

• these affects impact the hippocampus (dementia and alzheimers) and motorneurons (parkinsons disease)

glial cells act against this pathway by surrounding neurons and absorbing oxidants

Question 6

how does the super-oxide system affect the hippocampus in response to stress?

Answer 6

1. stress increases glucocorticoids (GC) which activate cytosolic GCRs (GCRs are insensitive ∴ require high levels of stimulus)
2. a) activated receptor immediately transolactes to nucleus to modulate gene expression through GREs (gluccocorticoid response elements)
   b) co-localize with the anti- apoptotic Bcl-2 protein and translocate into the mitochondria.
3. ↑’s mitochondrial MP , Ca2+ capacity, mitochondrial oxidation = ↑ metabolic rate = ↑ ATP synthesis + ↑ spontaneous super-oxide (O2-) via electron transport chain
4. manganese super-oxide dismutase (Mn-SOD) converts super-oxide —> hydrogen peroxide. hydrogen peroxide either further converted to highly toxic hydroxyl radical (OH-) OR reduced to water via mitochondrial antioxidant pathway
5. cytosolic super-oxide produced via the oxidation of NADPH. super-oxide converted to hydrogen peroxide by Cu ,Zn-SOD. hydrogen peroxide either neutralised by catalase (CAT) or glutathione peroxidase OR interacts with super-oxide or transition metals (Fe2+, Cu2+) to form highly toxic hydroxyl radical (OH-)
6. places oxidative stress of neurons and glial cells. neurons display a poor expression of endogenous antioxidants ∴ more vulnerable to oxidative stress.

Question 7

how does the nitergic system affect the hippocampus in response to stress?

Answer 7

1. stress induces release of glucocorticoids which activate mineral-corticoid receptors
2. increase in NMDA channel activity = ↑ influx of calcium = ↑ calmodulin = ↑ nNOS. nNOS converts L-arginine to L-citruline to produce NO
3. super-oxide + NO = ONOO-, which converts tyrosine to 3-nitro-tyrosine
4. ↑ NO + ONOO- inhibit electron transport chain = ↓ ATP = energy crisis
5. overtime as stress continues, nNOS↓ and iNOS (interstitial) ↑. Both forms of NO act as a neurotransmitter on pre-synaptic neurons
6. presynaptic NO causes glutamate release = post-synaptic NMDA receptors ↑ [Ca2+] and if calmodulin present, further potentiate nNOS produced NO
7. ↑ NO downregulates glucocorticoid receptor (neuroprotective mechanism) = hypothalamus stimulated to release GCRH —> destruction of neurons + depressive-like behaviour

Question 8

how does long-term stress affect the hippocampus?

how does this affect the amygdala?

Answer 8

hippocampus responds to high-level of cortisol by signalling hypothalamus to turn off cortisol-producing mechanisms

long-term exposure to cortisol accelerates degeneration of the hippocampus

damaged hippocampus ==> cortisol levels not regulated ==> further compromised memory and cognitive function

• cortisol exposure increases activity of glucocorticoid receptors
• this increases the activity of Ca2+ dependent K+ channels —> hyperpolarisation
• prolonged hyperpolarisation causes neurons to become less excitable, resulting in long-term depression
• under these conditions, the hippocampus reduces dendritic connections in an attempt to save it’s neurons
• loss of apical dendritic branch points and decreases in the length of apical dendrites
—> regression occurs in CA1 and CA3 cell fields of the hippocampus
—> process is slowly reversible (not so the older you get)

as stress causes atrophy of dendritic processes in hippocampus, same stress causes extension of neurons in amygdala + stria-terminalis
—–> enhanced aspects of implicit memories related to autonomic conditioning, implicit reflexes, and fear (anxiety)