LMBR8: SLEEP 1. P 259-269

Question 1

What are Components of endogenous or internal oscillators and location ?

BR 261

Answer 1

Endogenous oscillators include both the central and peripheral oscillators.

• Central oscillators: are found in the suprachiasmic nucleus (SCN) in the hypothalamus, which is the main body “clock”.
• Peripheral oscillators: are present in every major organ in body (kidney, liver, heart, adrenal glands and pancreas). They allow for synchrony and alignment between the central and peripheral clocks.

Question 2

What is Melatonin secretion is regulated by?

BR 261

Answer 2

Melatonin secretion is regulated by SCN (suprachiasmatic nucleus) – portion of hypothalamus

• triggered by DARKNESS

Question 3

What is the Sequence of events of entrainment (in context of circadian rhythm)

BR 261-2

Answer 3

Neural tract from retina to SCN =>SCN to pineal gland controls melatonin production =>splanchnic nerves innervate adrenal glands (regulate blood flow, temp and food intake thru hormones like epinephrine, norepinephrine, glucocorticoid and aldosterone)

Question 4

What is entrainment

BR 261-2

Answer 4

Entrainment - The ability to be brought into the rhythm.

Question 5

What is Responsible for awakening cortisol spike?

BR 263

Answer 5

SCN is responsible for awakening cortisol spike

Question 6

List 4 inputs which can change the circadian rhythm

BR 264

Answer 6

Inputs which can change the circadian rhythm:

Light - intensity, wavelength (esp blue - 480 nm)

Temperature - ambient

Food - mainly carbohydrates (eg pasta)

Fluids => blood osmolality (eg Na, K, Cl in plasma)

Mn: at La Spaghett

Question 7

What is melanopsin?

BR 263

Answer 7

Melanopsin is the photopigment in the Retinal ganglion cells and is the pathway that the SCN clock is entrained.

Question 8

Melanopsin is sensitive to which light?

BR 263

Answer 8

Melanopsin is maximally sensitive to short wavelengths of light (blue light, ~480nm).

Question 9

What is the cycle of stimulating the endogenous oscillators- arrange in order

BR 264-5

Answer 9

• see figure p 264

Question 10

What are PER & CRY ?

• what timeline do they operate over ?
• what causes more PER protein to be produced ?
• WHERE do PER & CRY act?
• what is the consequence of polymorphisms in these proteins ?

BR 264, here

Answer 10

• PER and CRY proteins controls the circadian rhythm throughout the body in the peripheral oscillators.
• PER and CRY inhibit function of other proteins (proteins “clock” and “cycle”) until they degrade, a process that takes approximately 24 hours.

- Exposure of retinal ganglion cells to light causes more PER protein to be produced, an important factor for “entrainment” of this molecular cycle.

• If single nucleotide polymorphisms occur in the PER and CRY proteins, these proteins may not be able to function appropriately, and the circadian rhythm in the body may not work.

Question 11

What triggers melatonin?

Events after melatonin secretion

BR 265

Answer 11

Melatonin secretion is triggered by darkness

Cutaneous vasodilation > extremity warming > cooling of core body temperature > sleep initiation

Question 12

Lowest core body temperature is reached in how many hours

BR 265

Answer 12

Lowest core body temperature is reached around 4 hours after sleep onset

Question 13

In early sleep what happens to blood pressure and sympathetic tone

BR 265

Answer 13

In early sleep see Decreased blood pressure and sympathetic tone

Question 14

EEG in early sleep

BR 265

Answer 14

Predominantly slow-wave on EEG

Question 15

What changes take throughout the sleep (3)

BR 265-6

Answer 15

R - Remodelling of DNA

A - fatty Acid metbolism

I - Increase in cortisol

L - Leptin secretion

Mn - Zzz - sleeping on a train on rails

Question 16

During what part of the sleep cycle is there more REM sleep ?

REM sleep is when __ extinguising occurs

BR 265

Answer 16

During later part of sleep cycle one sees longer REM periods (important for fear extinguishing).

Question 17

Changes seen in late sleep to awakening

Answer 17

Decreasing melatonin > increase core body temperature, cool peripheral skin, longer REM periods (important for fear extinguishing). Increased blood pressure and sympathetic tone, increase baroreceptor sensitivity

Question 18

When does Cortisol peak takes place

BR 265-6

Answer 18

Peak cortisol level in a 24-hour period occurs upon awakening. This spike is important in the transition from sleep to wakefulness.

Question 19

What is the Relationship between sleep - – melatonin, sleep propensity and core temp

BR 265-6

Answer 19

Melatonin and sleep propensity directly proportional to sleep and

Core temp is indirectly proportional to sleep – means cool core temp while sleeping

Question 20

What type of light most effects melatonin production

ie __ light => [melatonin]

BR 267

Answer 20

Blue light (420-480 nm) creates greater melatonin suppression at lower intensities and shorter durations

Question 21

What is the PREDOMINANT entraining force of the central SCN clock ?

Give egs of 4 aspects of this force which effect the SCN

BR 266

Answer 21

LIGHT is the predominant entraining force of the central SCN clock

Components of light which effect SCN:

a) Intensity
b) Spectra (ie Wavelength)
c) Timing of light Exposure in a 24 hr cycle
d) Duration of light exposure.
- Mn: WIDE

Question 22

What are the effects of low light intensity with daylight ?

BR 267

Answer 22

Low daylight

a) Decreases daylight activity, alertness, decreases positive affect and decreases core body temperature
b) Results in increased melatonin suppression with evening light (ie makes one more prone to insomnia from night time blue light)

=> delayed onset of sleep & shifting of the sleep cycle.

=> Indoor / Office workers are at risk for this.

Question 23

What are blue light effects (physiological)?

Sources of blue light

Effect of blue spectra with low intensity

Blue light causes delayed or advanced phase?

What does blue light do to sleep onset/cycle.

Blue light is like __ travel.

BR 267

Answer 23

• Blue light
  a) Increases nighttime heart rate, increase cortisol, blood pressure and core body temperature.
  b) Decreases sleepiness
  c) Suppresses melatonin
• Back-lit computers, TV screens, phones, and other screens (which have strong blue spectra components) have powerful melatonin suppressive effects even though the intensity may be low
• Blue light leads to delayed phase (like westward travel)
• Inhibits sleep onset and shifts the sleep cycle later

Mn: ‘Blue delay, like flying to LA”

Question 24

1) What do your understand by eastward and westward in relation to circadian rhythym ?
2) Name 3 things that can be done to help with jetlag

Front Physiol 2019:10:927

Answer 24

Immediately after westward flight, the circadian system will be running ahead of the local time zone. For example, after a flight from London to Los Angeles (8 h west), when the body clock is ready for bed at 23:00 London time, it will only be 15:00 in Los Angeles. To adjust to the new time zone, the circadian system has to delay, or shift backward, or move later.

Conversely, immediately after eastward flight, the circadian system will be running behind the local time zone. For example, after a flight from Los Angeles to London (8 h east), when it is time to get up at 07:00 in London, it is only 23:00 in Los Angeles, so the body clock will be ready for bed. To adjust to the new time zone, the circadian system has to advance, or shift forward, or move earlier.

Delays and advances in the timing of the circadian system can be facilitated by appropriately timed Light exposure, Melatonin ingestion, and/or Exercise

Mn: M.E.L. (Gibson w jet lag)

Question 25

Is SCN clock equal to 24hrs

Effects of sleep delay/disruption on:

a) Sleep
b) Daytime function
c) Metabolism

BR 268

Answer 25

• SCN clock: most have 24 hours and 8 minutes (delayed phase shift). In general, SCN needs to be reset forward (advanced) or reset backward (delayed) by five to 15 minutes a day
• Sleep delay leads to decreased

C - Calorie burning

T - core Temperature

A - Appetite increased

I- Insulin resistance

L - Leptin decreased

S - Sociability dec, REM Sleep decreased

P - Positive affect dec

A - Attention, Activity decreased

M - Melatonin decreased

Mn: David C-TAIL & SPAM

Question 26

Effect of carbohydrates on sleep

If person is falling asleep too early …

If person is falling asleep too late …

BR268

Answer 26

Low-carbohydrate breakfast lead to diminished cortisol awakening rise.

High CHO breakfast may improve sleep-wakefulness transition

Eating CHO will delay sleep

If someone is falling asleep too early, they can eat more carbohydrates at dinner

If someone is falling asleep too late, they can shift carbohydrates to earlier meals, avoid snacking and carbohydrate rich dinners and eat an earlier dinner

Question 27

Peripheral body temperature effect on onset of sleep

Behaviors which shunt blood from the __ to the __ and their effect.

BR 269

Answer 27

• If peripheral body is not warm enough during transition to sleep, sleep onset may be inhibited

Antecedents which shunt blood from the core to the periphery (help sleep onset):

Meditation

Autogenic training

Yoga,

Benzodiazipines

• all produce a similar effect in the body’s natural shift of heat to the extremities. With these antecedents, blood is shunted from the core to the extremities as sympathetic activation in the muscles and skin, heart rate and energy expenditure are all reduced. Thus help sleep onset.
• Mn: M.A.Y.Be shunting helps sleep.

Question 28

Populations that are more sensitive to melatonin suppression

Br269

Answer 28

=> those with decreased light on their retina & depressive (component) disorders (see figure)

Elderly with cataracts

See figure p 269

Mn - ‘Melatonin suppression => MAD’

• ‘MAD: Melatonin => Affective Disorder’

Question 29

In terms of retinal illuminance:

1) What is it ?
2) What happens to it as we age ?
3) Is it the same for all wavelengths of light ?

BR 269

Answer 29

Retinal illuminance:

1) = the amount of light reaching the retina (here)
2) Retinal illuminance decreases as we age (dec 50% from 10-45 yo, then another 50% to 65 yo)
3) Short wavelenghts (ie blue light) are most affected while longer wavelenghts (red light) are least affected.

Question 30

Is there a correlation between melatonin and mental disorders ?

BR 269

Answer 30

Melatonin suppression correlates with mood disorders (affective): Major depressive disorder, seasonal affective disorder, bipolar disordar

• ‘MAD: Melatonin => Affective Disorder’