Brain Systems for Energy Balance and Stress

Question 1

What is a basic way to consider this system?

Answer 1

We have either an inhibitory or excitatory drive that pushes you towards fasting or eating

This appetite control centre is localised to the hypothalamus where feeding behaviour can be promoted or inhibited

Question 2

What is leptin?

Answer 2

A hormone that is released when you have good energy stores, this is released from fat cells and inhibits feeding behaviour

Question 3

What is ghrelin?

Answer 3

A hormone that signals an empty stomach and the need to get food, this is released from cells of the stomach and GI system and promotes feeding behaviour

Question 4

What do mechanoreceptors in the GI tract sense?

Answer 4

Fullness- and they signal this to the brain via the vagus nerve

Question 5

When does insulin signal?

Answer 5

In relation to blood sugar levels

Question 6

What is a complication of feeding systems?

Answer 6

need to remember the objective is energy balance, so responses will also impact on metabolism (burning) of fat and autonomic nervous system actions to prepare for physical activity

Question 7

What context should we always remember?

Answer 7

The evolutionary context

The availability of food we have now and especially food that is dense in energy sources, so fats and sugars is something that our brain system and body is not adapted to

The balance of fasting and feasting is in the context of an evolutionary situation in which this resources are hard to get and whre these resources actually require a lot of energy expenditure to access

Question 8

What nucleus in the hippocampus is really important in energy balance and feeding behaviour?

Answer 8

The arcuate nucleus

Question 9

What is the arcuate nucleus?

Answer 9

Its a nucleus of the hypothalamus that is a key integrator for hormone signalling input

Its where the excitation/inhibition of feeding behaviour seems to reside

ARC projects to other hypothalamic structures and onwards into cortical and limbic circuits- the wiring is linked to emotion and other affective states, e.g. eating for comfort - we have a simple system of feed, fast, exercise, and dont expend energy, but it sits in the wider context of other brain systems

Question 10

What are the two drives in response to food?

Answer 10

Homeostratic
Hedonic

Question 11

What is food?

Answer 11

A primary reinforcer

Food, as a reinforcer, activates brain reward circuitry to establish a ‘linking’ for food alongside a ‘wanting’ as behavioural motivator

Question 12

Where do powerful motivational mechanisms for seeking and consumption of food come from?

Answer 12

Evolutionary pressures in the context of general scarcity of food as a key resource

Question 13

What underlies food reward and the hedonic drive?

Answer 13

Dopaminergic signalling from the ventral tegmental area to the nucleus accumbens

Question 14

What brain regions is the homeostatic drive linked to?

Answer 14

Lateral hypothalamus - integration of info from limbic system, linked to generation of different behaviour states

Arcuate nucelus- appetite regulating neurons

Question 15

What did Volkow et al. (2009) find?

Answer 15

Brain reward circuits can be activated by the same hormones that are key for homeostatic regulation

The paper also considers pathological aspects: food as an addictive substance and dysregulation of control circuits

Found strong activation of reward circuitry
–> Leptin decreases, whereas ghrelin increases, reward circuit responsivity to food stimuli

Basically when you’re hungry, due to an increase in grehlin and decrease in leptin, the brain actually likes food more

Question 16

What did Volkow et al. (2009) find about obesity?

Answer 16

In individuals with obesity, central rewards circuits responses that would normally light up strongly to palatable food stimuli are blunted, whereas primary somatosensory signalling related to palatability are enhanced

You’re not getting the same pleasurable response to food stimuli you may otherwise get which may partly explain increased seeking of those sorts of palatlbe food

Question 17

What is Oxytocin?

Answer 17

A love hormone– key for prosocial behaviours and bonding, now recent evidence suggests that it can modulate calorie intake

Question 18

How is oxytocin linked to food?

Answer 18

Released by hypothalamic neurons when food reward is known to be present and can modulate both hedonic and homeostatic pathways

One other mechanism of action may also be via reduced stress responses via downregulation of the HPA axis

Question 19

For the system to work effectivedly what do we need ?

Answer 19

Brain-body feedback loops

We need leptin to be able to cross the BBB to be able to signal to the hypothalamus about energy stores

Question 20

How can leptin be implicated in disease?

Answer 20

Chronically high levels of leptin can induce leptin resitence (resistence of leptin crossing the BBB)

Means the brain isn’t going to know to the same extent that the energy stores are all okay, so this drives a cycle of then increasing leptin levels, as more food is consumed

= a positive feedback loop as satiety signalling is increasingly impaired, which can lead to increased consumption of food, and further impairment of satiety signalling

Question 21

What is an important mechanism from chronically high leptin levels

Answer 21

Chronically high leptin levels can lead to impaired expression of leptin receptors and impaired signalling onwards from these receptors

This is an interesting mechanism that can explain why high leptin levels may be associated with overweight and obesity, and make the situation difficult to get out of

Question 22

How can cardivascular risk factors exacerbate chronically high leptin levels?

Answer 22

They cause inflammation related effects on the BBB which can make it even harder for leptin to cross the BBB and thus exacerbates these issues, as obesity is an inflammatory state affecting all tissues of the body- this is peripheral

Question 23

Why is the stress response important?

Answer 23

Mobilising bodily systems appropriately and rapidly in the event of an acute threat is of huge survival value

Question 24

What is important to the stress response?

Answer 24

Hypothalamus
Endocrine glands
Hormones

Question 25

What two primary pathways become activated in response to an acute stressor?

Answer 25

1. Sympathetic-adrenal-medullary pathway
2. Hypothalamic-pituitary-axis

In both cases the body is trying to achieve something adaptive

Question 26

What is an issue with the stress response system?

Answer 26

There are some things we encounter in modern times that the stress response system probably isnt well designed to cope with

e.g. high workload, sleep difficulty, screen use-

these create stressful siuations which persist over a long time where stress response systems can make long-term issues worse, they become less self-defensive- they’re more concerned with short-term e.g. removing you from harm or recovery from some sort of damage

Question 27

Stress is not just psychological, it is also what?

Answer 27

Physiological

e.g. low blood oxygen levels, tissue damage, disturbed metabolic function, inflammation etc

Question 28

What is the sympathetic-adrenal-medullary pathway?

Answer 28

For SAM activation, the hypothalamus projects via brainstem and spinal cord to activate sympathetic nervous system (“get ready for action!”)

Activation of the adrenal glands, and the adrenal medulla specifically, is a key component as causes the production of adrenaline

Question 29

What is adrenaline?

Answer 29

A circulating hormone (though also a neurotransmitter)

Acts in concert with other sympathetic nervous system effects

Question 30

What can adrenaline effect?

Answer 30

a1-Adrenergic receptor
Increases vasoconstriction
Decreases blood pressure

b1-Adrenergic receptor
Increases cardiac contraction force
Increases heart rate

b2-Adrenergic receptor
Increases bronchodilation

Question 31

What is an important issue with adrenaline?

Answer 31

Unlike most other circulating hormones, adrenaline does not have a direct negative feedback mechanism

In effect, requires absence of the stressor for reduction in levels

Question 32

What aspects of the sympathetic system are affected by the SAM pathway?

Answer 32

Pupils dilate
Heartbeat increases
Airways dilate
Sweating
Liver increases glucose production
Digestive system decreases activity
Bladder relaxes

Question 33

How can long-term activation of the SAM pathway affect health?

Answer 33

Chronic activation of this pathway can have negative effects, as some systems e.g. digestive system are vital to survial which gives us an understanding of how chronic activation can impair key digestive function and have other effects on bodily health and itself create stressors that can amplify the effects

Question 34

What is the HPA Axis pathway?

Answer 34

Hypothalamic activation causes release of cortisol (via anterior pituitary) from adrenal gland

Cortisol is released from cortex of adrenal gland

Question 35

What are the effects of cortisol?

Answer 35

Cortisol is mainly responsible for two things:

1. Elevation of glucose availability (breakdown of fat and protein)
2. Immune suppression/regulation

Other CNS effects too though, including reduced serotonergic function

Question 36

What is a postive aspect of the HPA Axis Activation system?

Answer 36

There is some negative feedback to bring this system back into check

Question 37

Describe how the stress response system is designed to handle transient stressors.

Answer 37

The system is setup to prepare the body to deal with an immediate and fairly short-term threat

Continuous activation of stress responses systems can have a range of undesirable systemic (e.g. cardiovascular) and neurological (e.g. cognitive, affective) effects

Many glucocorticoid receptors (which bind cortisol) in the hippocampus and activation of the amygdala has also been shown

HPA axis dysregulation is associated with major depression and reduced cognitive function

Probably occurs due to central (brain) reductions in sensitivity to circulating cortisol (as the critical negative feedback mechanism)

Sustained activation of stress responses systems is bad for the body as well as the brain – it can lead to cardiovascular and metabolic disease and related systemic inflammation – which themselves are biological stressors

Either ‘branch’ of the stress response can affect activity in the other, especially in the chronic stress situation

Question 38

What do brain systems controlling stress require?

Answer 38

stressor termination and/or negative feedback for effective (and healthy) operation