Exam 2 Flashcards
(185 cards)
1
Q
What was seen in patients who died of insomnia
A
Inflammatory lesions of the anterior hypothalamus
1
Q
What part of the brain is important for spindles and high amplitude slow waves
A
thalamus
2
Q
Describe the ascending arousal system in the brain.
A
Sensory inputs that are critical for wakefulness go from midbrain and brainstem (pons and medulla) to the cortex
3
Q
What does wakefulness depend on?
A
Activity of neurons within the brainstem and reticular formation
4
Q
Where is REM sleep located in the brain?
A
Pons (upper brainstem)
5
Q
Does wakefulness/sleep require input from the periphery?
A
no
6
Q
What is the Raphe nucleus
A
Produces serotonin which is important for the transition from wake to sleep
7
Q
What is the role of the hypothalamus in sleep?
A
Primary active NREM sleep promoting region
8
Q
Describe the role of each part of the brain in the control of wakefulness.
- Locus coeruleus, Raphe, vPAG, TMN, Lateral hypothalamus, basal forebrain, LDT, PPT
A
Locus coeruleus: norepinephrine important for arousal and attention
Raphe: seratonin in upper brainstem, promotes wakefulness, transition to sleep –> drugs that impact seratonin = effect REM sleep
vPAG: dopamine important for arousal
TMN: in hypothalamus, histamine (wake promoting neurotransmitter)
Lateral hypothalamus: orexin - stabilizes wakefulness–> activate REM off cells
Basal forebrain: ACh promotes wakefulness
LDT: ACh –> active during REM, inhibit REM off cells (one way)
PPT: ACh –> active during REM, inhibit REM off cells (one way)
9
Q
Which of these project to straight to the cortex vs going through thalamus?
A
LDT and PPT project to the thalamus and then to cortex, all others project straight to the cortex
10
Q
What is the PB?
A
Parabrachial complex: in the pons, uses glutamate which is an excitatory neurotransmitter that promotes arousal - is inhibited by GABA from the VLPO
10
Q
What is the VLPO/MnPO?
A
Median preoptic nucleus/ventrolateral preoptic nucleus: active sleep system in the hypothalamus - secretes GABA (dominant inhibitory neurotransmitter in the brain) which inhibits other neuron groups to promote sleep
11
Q
Which neuron groups are inhibited by the VLPO?
A
TMN, PeF, Raphe, vPAG, LC, PB, LDT, PPT (not BF)
12
Q
What is the PFZ?
A
Parafacial zone: in the medulla - promotion of SWS (NREM) by inhibiting PB
13
Q
How do the wake and sleep centers work together?
A
They mutually inhibit each other, whichever has stronger inhibition tells whether someone is awake or asleep
14
Q
What is adenosine?
A
Sleep promoting neurotransmitter
15
Q
Where and how does adenosine act?
A
Basal forebrain: inhibited by adenosine
Ventral lateral preoptic area (VLPO): excited by adenosine
Cortex: inhibited by adenosine
16
Q
Where does adenosine come from?
A
Byproduct of cellular metabolism (breakdown of ATP)
17
Q
How is adenosine involved in the control of sleep (general) and how was this discovered?
A
Involved in process S: builds up with time and dissipates with sleep
Discovered by measuring ECF in the basal forebrain of sleep deprived rats
18
Q
How do glia (astrocytes) contribute to sleep?
A
Need to deactivate glutamate to sleep. Astrocytes surround a synapse and when glutamate is released, it binds to the postsynaptic cell as well as astrocytes. This releases calcium and ATP which is converted to adenosine. Adenosine binds to inhibitory receptors on both neurons and inhibits them
19
Q
What is the result of this pathway with astrocytes?
A
Similar to negative feedback - can cause local sleep in these neurons (which can result in performance impairments)
20
Q
How does the SCN influence sleep/wake centers in the brain?
A
Has input to both
SCN enhances arousal during the day through input to the dorsal medial hypothalamus (DMH) which projects to arousal centers
SCN enhances sleep during the night by projecting to the VLPO
21
Q
What parts of the brain and neurotransmitters are important for NREM sleep?
A
Basal forebrain (GABA)
PFZ (GABA): SWS specifically
Anterior hypothalamus (5-HT): transition to sleep, initiates NREM
Immune factors (prostaglandins and cytokines)
Thalamus: sleep spindles and slow waves
22
Q
What parts of the brain and neurotransmitters are important for REM sleep?
A
Pons
Increase in acetylcholine
Suppression of NE, 5-HT, Hist (practically silenced)
23
How does REM affect emotion in memories?
REM strips emotion from memories
24
Which groups in the brain are essential to the REM-NREM sleep switch?
vlPAG/LPT (REM-off) and SLD/PC (REM-on) - both in the pons
25
How do these groups (REM-on vs REM-off) work together?
Mutually inhibitory using GABA: if REM-on is more active → have REM and vice versa
26
What else contributes to the REM-NREM sleep switch
VLPO: promotes REM by inhibiting REM-off
Lateral hypothalamus: releases orexin which activates REM-off cells
LDT/PPT: promote REM by inhibiting REM-off
LC/Raphe: activate REM-off cells
27
What is the pattern of firing during the transition from NREM sleep → wake?
Norepinephrine (LC) begins increasing → basal forebrain starts → transition occurs → VLPO stops immediately → TMN starts firing
28
What is the pattern of firing during the transition from wake → light NREM sleep?
LC and TMN quiet → VLPO starts → transition occurs → BF inhibited by adenosine takes longer to quiet
29
What can cause chronic insomnia?
Damage to the hypothalamus
30
How much effect does genetics have on sleep patterns?
Small to moderate genetic contributions
31
What is a cause of the genetic difference in sleep and what factors of sleep are affected?
Genetic variation of adenosine deaminase (breaks down adenosine) affects the duration and intensity of sleep in humans
32
Describe the effect of this genetic difference.
G/A population (small proportion) has much more deep sleep than the majority
33
What is the ADORA2A and how is it affected by genetics?
Adenosine receptor that is responsible for the effects of caffeine and modafinil (wakefulness promoting drug) - can have two haplotypes: HT4 and non-HT4
HT4 haplotypes are insensitive to caffeine but sensitive to modafinil, non-HT4 haplotypes are sensitive to both (increase performance and sleep is disturbed by caffeine)
34
Describe the data on the short sleep family.
Short duration of sleep with no negative effects due to a point mutation in the DEC-2 gene (transcriptional repressor), unknown whether there are long term consequences of less sleep
35
What genes affect obstructive sleep apnea?
Sleep wake genes, craniofacial morphology genes, ventilatory control genes, obesity genes, pleiotropic genes (i.e. leptin) - all increase risk
36
Describe the mammalian SCN clock gene model.
Process that takes ~24 hours
BMAL and CLOCK proteins bind to the promoter regions of Per and Cry genes in the nucleus to activate transcription → ribosomes in the cytoplasm translate the mRNA into two versions of PER and CRY proteins: one that’s large and stays in the cytoplasm and one that’s small and goes back into the nucleus → small protein binds to the BMAL/CLOCK proteins to remove them from the promoter (inhibit their own transcription) → eventually protein complex dissociates and BMAL/CLOCK can rebind
37
What is CK1ε and how does it fit into this process?
Enzyme that helps with translocation of PER/CRY protein complex back into the nucleus, also interacts with CLOCK and BMAL
38
How is BMAL produced?
Produced when RORa protein binds to its promoter (RORa is inhibited by REV-ERBɑ)
39
What happened when the SCN was removed and how was it measured?
Bioluminescence oscillated for a long time → shows SCN is truly independent of neural stimulation
Measured this way because when PER2 is produced, so is LUC → bioluminescence
40
How does the BMAL/CLOCK process compare with other species?
Many things on earth have molecular clockwork - players different but process similar
41
What is the clockwork due to?
Expression of genes/proteins have delays - coordinated delays create a molecular cycle
42
Describe the anatomy of the SCN.
Has inner core and outer shell - core sends info to the shell
43
Describe the neurochemistry of the SCN.
Photic info received by the core from the retina - use glutamate and PACAP (excitatory) → 2 dominant peptides in the SCN (AVP, vasoactive intestinal peptide (VIP)) that are important for communication within the SCN → SCN neurons are GABAergic - allows coordinated firing to sync with eachother
44
How does light affect the neurochemistry of the clock cycle?
Light induces expression of the PER gene and CLOCK gene
45
What is the importance of the shell of the SCN?
Important in phase advance/delay
46
How does caffeine affect the circadian clock?
Causes a phase delay - lengthens circadian period through ADORA1 receptors
47
What are ADORA1 receptors?
Adenosine receptors, levels show circadian rhythm
48
How does caffeine affect ADORA1 receptors?
Acts as an inverse agonist (causes the opposite effect) → increases intracellular cAMP
49
What are the PER34//4 and PER35/5 polymorphisms?
Repeated sequence of DNA, PER34/4 repeated 4 times, PER35/5 repeated 5 times
50
Did PER34//4 and PER35/5 have differences in PER3 RNA, melatonin and cortical levels (circadian markers) across the day?
No
51
What was different between PER34//4 and PER35/5 subjects?
The shorter allele (PER34/4) of PER3 is related with delayed sleep phase syndrome (DSPS) and eveningness whereas the longer allele of PER3 (PER35/5) is related with early morning type.
Greater performance decrement during the biological night in PER35/5
52
Describe familial advanced sleep-wake phase disorder?
Very early sleep onset: 4 hour advance of the sleep/wake cycle - autosomal dominant, highly penetrant, higher rates of occurrence in seniors, 1% of adults have it
53
Describe delayed sleep-wake phase disorder?
Delayed sleep onset, may have a genetic component, higher occurrence in younger adults, associated genes include AA-NAT (rate limiter of melatonin production) and CK1e
54
How do the majority of sleep promoting drugs work?
By GABA
55
What is the most common sleep promoting drug?
Zolpidem (brand name Ambien)
56
How does Zolpidem (Ambien) affect the GABA receptor?
Causes greater effect when GABA binds - increases GABA binding and hyperpolarization
57
Describe the GABA receptor.
Pentomeric receptor (GABA binds between the ɑ and β subunits, chloride channel - when opened, chloride flows in and hyperpolarizes the cell to inhibit it
58
What is the issue with affecting GABA receptors?
GABA receptors are all over the brain - affect more than the sleep wake system and have broad side effects
59
What do barbiturates do and what makes them dangerous?
Muscle relaxants - act like GABA and open channels - dangerous if used with alcohol
60
What are the risk factors for falls?
Biological factors, environmental factors, sleep problems (frequency of waking up at night, untreated insomnia, nocturia), use of sleep medications, daytime naps (indicates sleep issue)
61
How do sleep drugs affect fall risk?
Major increase in risk even with drug that has the least risk of falls
62
How do sleep drugs affect sleep inertia?
They make it worse, more of a cognitive effect in young adults than older adults
63
What is the effect of exogenous melatonin on daytime and nighttime sleep?
Daytime sleep: dose dependent effects improving sleep efficiency
Nighttime sleep: only improves latency to sleep, but not sleep quality
64
What are the cutoffs for a natural dose of exogenous melatonin?
<0.5mg is similar to natural levels, greater than that is not
65
At what age are melatonin levels highest?
Right before puberty
66
What are the effects of Ramelteon (melatonin agonist) on sleep?
Shortens latency to sleep at night, little influence on WASO at night, and improves daytime sleep (sleep efficiency and total sleep time)
67
When can caffeine affect nighttime sleep?
From 6 hours before bedtime to bedtime
68
What are the effects of caffeine on each factor of sleep?
Total sleep time:
Latency to sleep:
SWS and SWA:
REM sleep:
Daytime sleep:
Total sleep time: reduced
Latency to sleep: increased
SWS and SWA: reduced
REM sleep: no effect
Daytime sleep: greater disturbance
69
Are the effects of caffeine on sleep dose dependent?
yes
70
What is the effect of amphetamines on sleep and how do they work?
More disrupting to sleep than caffeine, work by release of excitatory neurotransmitters
71
What is modafinil and what are its effects on sleep?
Treatment for sleep disorders - increases latency to sleep, no measurable effects on sleep
72
What are the effects of alcohol on sleep?
Helps you fall asleep, but decreases sleep quality
Reduced latency, increased WASO, dose dependent suppression of REM, increased total sleep time, tolerance and withdrawal
73
What are the effects of marijuana on sleep?
Acute:
Chronic:
Withdrawl:
Acute: reduced sleep onset latency, increased SWS, reduced REM
Chronic: reduced SWS
Withdrawal: increase latency, WASO, PLMS; reduce SWS, TST; varying effects on REM
74
What are the effects of cocaine on sleep?
Sleep disturbance during use and withdrawals
75
What are the effects of MDMA on sleep?
Longer sleep latency, less REM
76
What are the effects of antidepressants on sleep?
Decrease REM sleep
76
What are the effects of major depression and schizophrenia on sleep?
Decreased SWS, less sleep continuity, decreased REM latency
77
What are the effects of antipsychotics on sleep?
Increased sleep continuity
78
What are DORAs and what are their effects on sleep?
Dual orexin receptor antagonists: decreased sleep onset latency, increased total sleep time, increased REM
Dose dependent improvement of sleep efficiency
79
Does the time of day you take a drug affect its effectiveness?
Yes - circadian influence on many drugs and their effectiveness
80
What is an example of when medication taken effects the response ?
Blood pressure medication should be ingested at bedtime/evening → much better effects
81
What affects our arousal thresholds?
Sleep stage, time of night, sleep deprivation, age, sensory system
82
How does sleep stage affect arousal thresholds?
Deeper sleep = larger stimulus needed to arise
N3/4 is hardest to wake from (highest arousal threshold), REM and N2 are second, N1 has lowest arousal threshold
83
How does time of night affect arousal thresholds?
Arousal thresholds are higher during the second half of the night, increase as night goes on
84
How does sleep deprivation affect arousal thresholds?
More sleep deprivation results in more SWA and therefore higher arousal thresholds (higher across the whole night) - affects both behavioral responses to stimuli and sleep disturbance
85
How does age affect arousal thresholds?
Highest threshold when 12 years old, decreases as we age, elderly adults easiest to awaken
86
How does taking a deep breath affect sleep?
Sleep spindle in SWS after a tone - coincides with the deep breath
87
Does the brain respond more to some info than others during sleep?
Responds more to important information such as our own names or own baby’s cry - shows we can distinguish during sleep, higher emotional response to important info too
88
Describe how environmentally induced disruptors (cars, planes, etc) affect our sleep (general).
Dose dependent: louder stimulus = more likely arousal
Brief arousal is associated with body response (increase in HR)
Many disruptions are brief - not fully awake
89
Describe how environmentally induced disruptors affect the factors of our sleep.
Slower reaction time, less SWS, worse subjective sleep
90
Is there habituation over time with more exposure to sleep disruptors?
no
91
At what volume will most adults awaken?
~ 60 dB
92
How does alcohol affect response to fire alarm signals?
Higher arousal threshold with more alcohol intoxication
93
How did a T3 alarm affect sleep as compared to a normal smoke detector?
A T3 alarm had a different pattern of beeps and worked better to awaken
94
How do flurazepam and pentobarbital affect sleep?
Increased arousal threshold
95
How does caffeine affect arousal thresholds?
Decreases it
96
What is the effect of odors on sleep?
Any odor disrupts sleep: more brief awakenings, more behavioral responses, more EEG speeding
97
Did people sleep better to heavy metal or classical music?
Heavy metal because less changes within the music - more consistent
98
What is the effect of nociception on sleep?
Sleeping on a hard surface, cold stimuli, and heat pain are disruptive
Pain is disruptive to sleep, sleep loss increases sensitivity to pain → vicious cycle
99
How does muscle atonia occur during REM?
REM sleep hyperpolarizes motor neurons - inhibitory GPs cancel strength of excitatory Graded potentials → signal at trigger zone too weak → no AP produced
100
What is REM behavior disorder?
Lose muscle atonia and act out dreams
101
Describe the neurophysiology of the switch to REM sleep.
The SLD (REM-on center) both excites an inhibitory interneuron with glutamate and excites the SOM (in medulla) with glutamate which then excites an inhibitory interneuron also with glutamate → interneurons inhibit motor neurons using GABA and glycine
102
What are behaviors associated with REM behavior disorder (RBD)?
Choking/headlock of bed partner or caregiver, defenestration (throwing something/someone out the window), diving from bed
103
What does muscle tone look like during RBD vs normal?
Normal: not complete muscle atonia - range from ~75% - 100%
RBD: can see muscle atonia only <20% of the time → much more activity
104
What is the difference between symptoms in Parkinson’s patients in REM sleep and what does it show?
More articulate, smoother movements (improvements in motor function and parkinson’s symptoms) → shows that the symptoms they have while awake aren’t permanent
105
What is the correlation between RBD and neurodegenerative disorders?
RBD is an early biomarker for neurodegenerative disease - muscle atonia is a brainstem function so loss of this shows that the neurodegenerative disease hit that part of the brain and may progress higher later
106
How is RBD treated?
3-12 mg melatonin at bedtime or clonazepam (benzodiazepine)
107
What are RLS and PLMS and their connection?
Restless leg syndrome (during the day) and periodic limb movement syndrome (during sleep) - often occur together
108
Describe RLS.
Unpleasant sensations in their legs with an urge to move, growing pains in children, more common in women and older adults
109
What are the diagnostic criteria for RLS?
An urge to move the legs with uncomfortable sensations - worsens during rest/inactivity, relieved by movement, worse in the evening or night
110
Describe PLMS.
Frequent, periodic, involuntary jerking of any limb (more common in legs) during sleep, occur about every 30 seconds
111
What are potential causes for RLS?
Primary RLS: family history, may be genetic; unrelated to other disorders
Secondary RLS: associated with other medical conditions (pregnancy, iron deficiency anemia, end stage renal disease)
112
Do RLS or PLMS have a circadian influence?
Yes - RLS symptoms more in the evenings or night and are worse or only present at rest
113
What are the treatments for RLS/PLMS?
Lifestyle recommendations: remove caffeine, stop smoking, physical activity
Physical modalities: stretching, yoga
Other therapies
Medications
114
What medications are available for RLS?
Try iron vitamins first, then dopaminergic agents (dopamine involved in movement) and hypnotics (sleep promoting medications)
115
Describe sleep paralysis.
Feeling of being conscious upon awakening but unable to move due to muscle atonia continuing from REM: only an issue if there are other symptoms, can include hallucinations
116
Who does sleep paralysis affect?
Anyone, most often individuals with narcolepsy or sleep apnea, or as a result of sleep deprivation or shift work, typical onset in teens, no sex differences
117
How is sleep paralysis treated?
Education about REM and muscle atonia; if other symptoms: rule out narcolepsy, adopt healthier sleep habits, tricyclic antidepressants can help in more serious cases, cognitive-behavior therapy
118
What are some other rhythmic movement disorders?
Nocturnal groaning (catathrenia): don’t treat
Head banging during sleep: against arm or pillow like at a concert
Seizures during sleep: seizures more likely during sleep, need to rule out other diagnoses
119
Describe sleep/circadian regulation of core body temperature.
Circadian rhythm but is still impacted by sleep/wake
120
Describe sleep/circadian regulation of melatonin.
Completely circadian driven → primary marker of master clock
121
Describe sleep/circadian regulation of cortisol.
Strongest influence by circadian rhythm, still influenced by sleep (reduces cortisol at beginning of night) and wake (causes a spike)
122
Describe sleep/circadian regulation of urine volume.
Fluid input is constant but output is not: circadian and sleep wake regulation
123
Describe sleep/circadian regulation of TSH.
Circadian rhythm (high during the night, low during the day) and sleep influence (reduces levels)
124
Describe sleep/circadian regulation of growth hormone.
Sleep induced and regulated (increases with sleep)
125
Describe sleep/circadian regulation of prolactin.
Sleep induced and regulated (increases with sleep)
126
Describe sleep/circadian regulation of PTH (parathyroid hormone).
Sleep induced and regulated (increases with sleep)
127
How do growth hormone levels change over the day/night?
Large spike during the first half of the night - connected to SWS
128
How does the SCN affect adrenal glands?
2 ways that SCN regulated cortisol to prepare body for wakefulness
1. Activates CRH release from the hypothalamus
2. Has a neural connection to the adrenal gland to impact rhythm
129
What is the daily pattern of cortisol levels?
Lowest at the beginning of the night, increase throughout the night → circadian driven
Spike after wake → some sleep driven
130
What is the effect of sleep deprivation on growth hormone levels?
No large bouts of growth hormone like you normally see
131
What is the effect of recovery sleep on growth hormone levels?
Recovery sleep → more SWA → more growth hormone
132
What is the effect of sleep deprivation on cortisol levels?
No sleep induced decrease in the first half of the night
133
What is the effect of sleep deprivation on TSH levels?
More TSH with total sleep deprivation, suppression in TSH with sleep restriction (4hrs for 6 days)
134
How are BMI and sleep duration related?
Lowest BMI with 7.5-8.5 hours of sleep - higher BMI with more or less
135
How does short sleep duration affect obesity levels in children and adults?
Greater risk in adults, much greater risk in children
136
What parts of the brain are involved in feeding?
Arcuate nucleus of the hypothalamus: NPY/AgRP stimulate appetite, POMC/CART suppress appetite
137
What is leptin?
From white adipose tissues, represents fat stores, inhibits food intake
138
What do leptin levels look like throughout the day/night?
Peaks in the first half of the night
139
What is ghrelin?
From the stomach, promotes food intake
140
What do ghrelin levels look like throughout the day/night?
Decrease after each meal, increase before each meal, peak during sleep
141
What is PYY?
Peptide YY - acts like leptin and inhibits food intake, from L cells of the small intestine
142
What do PYY levels look like throughout the day/night?
Higher during the day, lower at night
143
How does inadequate sleep affect leptin levels?
Same pattern but overall lower leptin → increases appetite
144
How does inadequate sleep affect ghrelin levels?
Increases ghrelin which increases appetite and hunger → increase in food intake
145
How does insufficient sleep affect energy expenditure?
Increases energy expenditure during normal sleeping/nighttime hours → signals for more energy intake
146
How does insufficient sleep affect food intake for each meal?
No difference for any meal except post dinner snacks - eating later at night is associated with more weight gain because increase in intake with sleep deficiency is much greater than increase in energy expenditure
147
How does insufficient sleep affect weight loss?
Similar amounts of weight loss but loss occurs with fat free mass much more
148
What is the effect of inadequate sleep on glucose levels?
Higher glucose levels with insufficient sleep → impairment in insulin sensitivity → need to produce more insulin → contribute to risk of type II diabetes
149
How does sleep loss contribute to insulin insensitivity?
Impairs body’s fat cells to respond to insulin → can’t regulate blood sugar levels
150
What are the effects of a CLOCK mutation that results in arrhythmic sleep?
Higher energy intake with both regular and high fat diet, more weight gain, greater food intake during the dark phase, no difference in energy expenditure
151
What is the effect of circadian misalignment (shiftwork) on blood glucose management?
Higher glucose levels and insulin levels
152
What is the rhythm in insulin sensitivity over the day?
Fat cells are more insulin sensitive in the morning and less in the evening/night
153
Describe the experiments involving circadian misalignment.
2 conditions: circadian alignment (sleep during biological night but not enough) and circadian misalignment (sleep deprived the same amount but sleep at different times)
154
Which condition was worse for blood sugar regulation?
Circadian misalignment
155
What is hsCRP and how was it affected by circadian misalignment vs alignment?
High sensitivity C reactive protein: marker of inflammation - higher levels = less healthy chronically → more inflammatory
Higher with circadian misalignment
156
What was the effect of exogenous melatonin on insulin sensitivity?
Glucose levels higher after melatonin → results in reduced insulin sensitivity
157
What genetic variant is associated with increased risk of type II diabetes and where is it?
MTNR1B (melatonin receptor), expressed in beta cells of the pancreas
158
How does this genetic variance affect the effects of exogenous melatonin?
Produces even higher glucose levels - greater impairments on insulin sensitivity
159
How does timing of food intake affect weight loss?
How does timing of food intake affect weight loss?
160
an orexin agonist inhibits REM or NREM
inhibits entry into REM
161
Explain the 6 steps of the cellular timekeeping mamalian core clock genes
1. CLOCK-BMAL1 are positive Activators that bind to promoters of PER and CRY
2. Transcription of Per and Cry genes
3. Translation of Per and Cry proteins
4. Dimerization of Per-Cry proteins
5. Translocate back into the nucleus and interact w/ BMAL and CLOCK
6. PER and CRY dimerized inhibts (negative feedback) on BMAL and CLOCK binding
162
What is the hardest stage to wake up out of (highest arousal threshold)
stage 3
-- harder in second half of night to wake out of stage 2
163
How does odor disrupt sleep
any ordors disrupt sleep
164
do people sleep better in heavy metal music or classical
heavy metal b/c less change in noise dB
165
Explain what a Per gene does
* Per genes encode for proteins known as PERIOD proteins
* accumulate in cell during the night and degrade during the day
* interact with other CLOCK genes to inhibit their own transcription --> negative feedback loop that regulates circadian rhythm
* Period proteins are crucial in determining period length of circadian rhythm
166
Explain what a Cry gene does
* Cry genes encode for proteins called CRYPTOCHROMES
* Cryptochromes are involved in sensing light and transmitting this information to the circadian clock.
* They are responsible for resetting the clock in response to light cues, particularly blue light.
* Cryptochromes also interact with other clock proteins, such as PERIOD proteins, to regulate circadian rhythm.
167
What is the function of Per and Cry genes acting together
Per genes primarily involved in timing mechanism through regulation of PERIOD protein levels --> Cry genes play role in light sensing and resetting the clock
168
Explain what CK1ε is
enzyme that plays role in regulating circadian rhythms
* key in phorphorylation of key circadian clock proteins
* mark them for degregation
* phosphorylation of PER proteins essential in negative feedback the controls circadian rhythm
* phosphorylation of CRY influence function of clock mechanism
169
How do PER and CRY genes regulate the circadian rhythm
play role in regulating the timing and duration of circadian rhythm -- circadian clock synchronozed w/ environmental cues -- light-dark cycles = adapt to their environment
170
How does daylight savings time affect risk of heart attack?
Increases it in the spring for the first 7 days due to loss of sleep, decreases it during the fall
171
How does daylight savings time affect risk of stroke?
Overall rate of ischemic stroke was 8% higher during the first two days after transition, risk was higher for those with cancer and over 65 years old
172
What is ANS activity modulated by?
Transition from wakefulness to sleep, normal architectural changes associated with the sleep cycle, circadian phase, sleep disorders
173
What is blood pressure dipping?
The normal process of higher blood pressure during the day and lower during sleep. Less dipping at night is associated with more WASO and higher risk
174
What time of day is risk for heart attack and stroke the greatest?
In the morning
175
What time of day is systolic blood pressure the lowest?
In the morning hours after wake - associated with a higher risk of cardiac events - driven by circadian rhythm
176
When is the highest risk of fainting?
Middle of the night - circadian driven
177
Are cardiovascular genes expressed rhythmically?
Yes due to the CLOCK gene
178
What does sympathetic tone look like in REM and non REM sleep?
Decreased in non REM, increased in REM (burst)
179
How does insufficient sleep affect vasodilation?
Impairs the ability to vasodilate - dependent on nitric oxide, less increase in blood flow
180
How does sleep affect hypertension?
Sleep can improve blood pressure regulation → reduces hypertension
181
What is the effect of exogenous melatonin on blood pressure?
Melatonin causes peripheral vasodilation → reduces blood pressure
182
What happened when cardiomyopathic hamsters were misaligned?
Chronic circadian misalignment reduced the survival time of the hamsters → earlier death
