Rhythms and sleep Flashcards
1
Q
How have organisms on earth adapted to the 24 hour changes in their environment?
A
environment by developing biological rhythms
2
Q
What are the different types of cellular biological clocks?
A
- Cell cycle progression
- DNA damage repair
- Cellular energy metabolism
- Cell detoxification
- Neuronal excitability
3
Q
What are the different types of physiological biological clocks?
A
- Sleep/wake
- Body temperature
- Cardiac output
- Memory
- Energy metabolism
- Eating behaviour
- Immune response
- Detoxification
4
Q
What types of disease are defects in our biological clocks associated with?
A
- Affective disorders (bipolar depression)
- Sleep disorders
- Neurodegenerative disease (e.g. Alzheimer’s)
- Obesity/ metabolic syndrome
- Inflammation (asthmas, COPD)
- Cancer
5
Q
How do modern lifestyles oppose our natural rhythms?
A
- Chronic shift work (-15M people in EU)
- Sleep deprivation
- Altered eating habits
- Jet Lag
6
Q
When our biological clocks go wrong what type of effects will it have?
A
- circadian rhythm disruption
- mental health effects
- CVD disorders
- Reproductive effects
- Brain effects
- GI disorders
- increased risk of cancer
7
Q
What are circadian rhythms and give examples
A
daily frequency (around 20-28 hours)
Sleep wake rhythms
Body temperature
8
Q
What are ultradian rhythms and give an example
A
less than 20 hours
E.g. heart rate
9
Q
What are circalunar rhythms and give an example
A
monthly
E.g. periods
10
Q
What are circannual rhythms and give an example
A
annual/seasonal
E.g. migration of birds
11
Q
Give features of the mammalian circadian system
A
- Self-sustained oscillator (can keep ticking forever by itself)
- With a period of around 24 hours
- Entrained by environment (light is the biggest factor)
- Driving rhythmical outputs
12
Q
Give features of the suprachiasmatic nucleus (SCN)
A
- Principle biological pacemaker
- In hypothalamus
- Directly connected to eyes through retinhohypothalamic tract (RHT)
- Signal from daily light cycle transmitted to SCN via RHT
13
Q
How is the SCN organised and how does it work?
A
- Pair of nuclei
- Situated side by side
- Around 10,000 neurones each
- Information coming from RHT reaches the base (core) of the SCN
- The core SCN will process the information, adjust the circadian rhythm accordingly, then send this information on to the shell SCN
- The shell SCN will then projections to other parts of the brain which will then send the information to other organs in the body
14
Q
What are neuropeptides used by?
A
Neuropeptides are used by neurons to communicate with each-other
15
Q
What neuropeptides are found in the core (ventrolateral SCN) and what is it’s function?
A
- VIP (vasointestinal polypeptide)
- Receive input from eyes (RHT)
16
Q
What neuropeptide is found in the shell (dorsomedial SCN) and what is it’s function?
A
- AVP (arginine vasopressin)
- Send output to other brain areas
17
Q
What is the molecular clock?
A
A bunch of clock genes expressed in a rhythmic fashion
18
Q
Talk about the pineal gland and melatonin
A
- Melatonin is secreted by pineal gland which is indirectly connected to the SCN
- The precursor to melatonin is tryptophan
- Melatonin = the hormone of sleep
- Melatonin is secreted during the night but inhibited in daylight
19
Q
In addition to the brain where else is circadian expression of clock genes found?
A
Throughout the body
20
Q
What does the circadian timing system do?
A
synchronises clocks across the entire body to adapt and optimise physiology to changes in our environment
21
Q
What does the SCN do?
A
SCN is the master pacemaker – it synchronises all the clocks in all the cells
22
Q
Where else can you find rhythms?
A
in disease, e.g. someone suffering pain in arthritis is worse in the afternoon
23
Q
What is chronopharmacology?
A
the study of:
- The manner and extent to which the kinetics and dynamics of medication are affected by endogenous biological rhythms
- How the dosing time of medications affects biological timekeeping and features (e.g. period, amplitude) of biological rhythms
24
Q
What does cancer chronotherapy show?
A
- Time of best tolerability coincides with time of best efficacy
- Conventional chemotherapy considers that the worse the toxicity experienced by the patient, the better the overall survival. However, this concept seems wrong for chronotherapy, where better survival rates are found among patients who do not experience toxicity
25
What is Oxaliplatin?
the first cancer chronodrug
- First anticancer drug to undergo chronotherapeutic development (circadian vs constant rate)
- Constant rate: 10 times higher incidence of neutropenia and distal paesthesias, 55% higher vomiting
- The mean dose of oxaliplatin and its maximum tolerated dose could be increased by 15% if fiven in a circadian rhythm-modulated rate
- Oxaliplatin now approved for colorectal cancer
26
What is lithium used for and what does it effect?
- Lithium is the first-line treatment for bipolar disorder
- Lithium affects the expression of numerous circadian genes, including activation of Clock transcription
- Lithium causes period lengthening and phase delay of the sleep-wake and body temperature rhythms
27
What does bright light therapy target and what are it's benefits?
- Target conditions: mood disorders (SAD, unipolar and bipolar depression), also in elderly, AD, jet lag, insomnia
- Benefits: improved mood, enhanced sleep efficiency, can take a few weeks to show benefit
28
Why is sleep necessary?
- Basic homeostatic need
- Important for learning and memory, growth and repair
- Studies where Ps stay awake for a very long time show that they suffer from performance deficit
29
What are problems associated with sleep deprivation?
- Cognitive impairment
- Performance impairment
- Immune system impairment
30
What is the structure of sleep?
- REM sleep and non REM sleep stages
- On initiation of sleep an individual will pass down stages 1-4 of NREM sleep and then rapidly have REM sleep
- On an average night we have about 5 cycles of REM and NREM sleep (each cycle is about 70 mins)
- NREM stages 3 and 4 are also called slow wave sleep (deep sleep)
31
How was the brain control of sleep discovered?
- Discovered at start of 20th century due to epidemic of disease Encephalitis Lethargica which affected millions of people in Europe and North America after WWI
- Only 1/3 patients made full recovery
- Patients slept > 20 hours/day
- Causing virus never identified. Last case reported in the 1930s
- Patients had lesions at the junction of the midbrain and diencephalon
- Von Economo proposed the existence of an arousal system originating in the brainstem
32
What areas are involved in circadian rhythms?
SCN, subparaventricular and dorsomedial areas (located in the hypothalamus)
33
Where is the VLPO found and what does it do?
- found in hypothalamus
| - induces sleep
34
What structures in the pons are involved in wakefulness?
LDT, PPT, Raphe and LC (Locus coeruleus)
35
What structure in the hypothalamus is involved in wakefulness?
The lateral hypothalamic area (LHA)
36
What is the 'flip-flop switch' model?
- When we are awake the alerting areas of the brain are most active and inhibit activity of other brain areas that promote sleep
- When the sleep promoting areas of the brain are most active they inhibit the activity of the wakeful areas
- We normally change from one stable state to another from changing influence from our biological clock and build up of need of sleep
37
How is the circadian rhythm of sleep and temperature controlled?
- SCN projects to the SPZ which then projects to the MPO which is involved in thermoregulation
- SCN also projects to DMH which projects to the PVH which controls sleep, DMG also projects to the LHA which controls wakefulness
38
What is our sleep drive?
- It is always present and growing while we are awake
- It is a homeostatic mechanism
- When we remain awake for an extended period of time structures in our brain promote sleep
39
What is the Circadian alerting system?
- After about 4 hours of uninterrupted sleep our sleep drive is decreased
- The internal clock which promotes alertness during the day sends signals to parts of the brain that make you sleep
- Circadian clock sends signals such as high levels of melatonin and decrease in body core temperature to increase it is time to sleep. The opposite happens in the morning to indicate it is time to wake
40
What governs sleep and wakefulness?
The interaction between the homeostatic drive to sleep and the circadian alerting signal
41
What external factors influence sleep?
- Light: both directly (make it hard to fall asleep) and indirectly (influences timing of internal clock)
- Jet Lag
- Shift Work
- Pain (usually just have light sleep), stress, medical conditions
- Medications
- Other substances such as coffee
- Alcohol helps sleep, however, it compromises the quality of sleep
- Alcohol worsens sleep apnea
- Sleep environment (bedroom environment): light, noise, temperature
42
What is Narcolepsy and why does it occur?
* Narcolepsy is a chronic sleep disorder in which people suffer from profound daytime sleepiness causing them to fall asleep at inappropriate moments
* It is caused by disruptions to the brain’s orexin pathways
* Orexin exerts a major influence in the flip-flop model of sleep/wake states
* Orexin is a neuropeptide produced by a small number of neurones in the hypothalamus and acts on a GPCR called Hcrtr2 in its target tissues.
* In most cases of human narcolepsy, the cause is thought to be an autoimmune attack of orexin producing neurons, resulting in their destruction.
43
In what other animal can narcolepsy be found and how is this different?
* Narcolepsy also occurs in dogs and can be inherited
* The canine narcolepsy has a different cause to the human version – it results from a premature stop codon in the Hcrtr2 receptor, which makes the receptor non-functional
