Circadian Rhythm Flashcards
what is circadian rhythm?
diurnal cycle that oscillates expression of circadian driven genes depending on the presence or absence of external factors
what are the factors of circadian rhythm + nickname for them
(zeitgeber)
- light (solar/synthetic)
- nutrients
- temperature
where is the central circadian clock machinery found + what’s it connected too + associated hormones
in the hypothalamus within the suprachiasmatic nucleus (SCN)
connected to the optic nerve and pituitary gland
leptin, follicle stimulating hormone (FSH), luteinizing hormone (LH)
to get from SCN to heterodimerization what 2 acronyms are used
CLOCK
(Circadian Locomotor Output Cycles Kaput)
BMAL1
(Brain and Muscle Arnt Like 1)
what is the Clock-BMAL1 heterodimer do + where does it bind too and where is it located
binds to an enhancer box (E-box) located on the nuclear membrane
promotes transcription of the period (PER) and cryptochrome (CRY) genes
also promotes transcription of retinoic acid receptor related orphan receptors (ROR) and REV-ERB which bind to ROR-response elements (RORE)
what does ROR do
promotes transcription of BMAL1 while REV-ERB represses it
central clock machinery summary describe it to me
within the SCN
- heterodimerization Clock and Bmal1
- BMAL1&Clock binding to E-Box
- translating for Per and Cry proteins -> negative feedback loops
- ROR and REV-ERB -> Negative/positive feedback via BMAL1 transcription
how does melatonin help physiologically with circadian pathways
- absence of light allows photosensitive retinal ganglionic cells (pRGC) to hyperpolarize allowing for the pineal gland to make melatonin
- melatonin is synthesized from the essential amino acid Tryptophan
Give me the diagnosis criteria for insomnia disorder 3 symptoms
A) a predominant complaint of dissatisfaction with sleep quantity or quality, associated with 1+ of:
1) difficulty initiating sleep
2) difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings
3) early-morning awakening with inability to return to sleep
what does GABA-A receptor do
- GABA is a major inhibitory neurotransmitter
- neuronal inhibition by increasing chloride ion conductance
- inhibits brain regions involved in wakefulness
additional components to diagnostic criteria for insomnia other than 3 symptoms
B) sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioural, or other important areas of functioning
C) sleep difficulty occurs at least 3 nights per wk
D) sleep difficulty is at least 3 mo
E) sleep difficulty occurs despite adequate opportunity for sleep
F) insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder
G) insomnia is not attributable to the physiological effects of a substance
H) coexisting mental disorders and medical conditions do not adequately explain the predominant complaint of insomnia
Symptom diagnostic criteria for hypersomnolence disorder
self reported excessive sleepiness despite a main sleep period lasting at least 7 hrs with at least 1+:
1) recurrent periods of sleep or lapses into sleep within the same day
2) a prolonged main sleep episode of more than 9 hrs per day that is nonrestorative
3) difficulty being fully awake after abrupt awakening
other diagnostic criteria for hypersomnolence disorder
B. the hypersomnolence occurs at least 3x per wk, for at least 3 mo
C. hypersomnolence is accompanied by significant distress or impairment in cognitive, social, occupational, or other important areas of functioning
D. hypersomnolence is not better explained by and does not occur exclusively during the course of another sleep disorder
E. hypersomnolence is not attributable to the physiological effects of a substance
F. coexisting mental and medical disorders do not adequately explain the predominant complaint of hypersomnolence
diagnostic criteria for narcolepsy
A. recurrent periods of an irrepressible need to sleep, lapsing into sleep, or napping occuring within the same day. must occur 3x/wk over past 3 mo
B. need one of the following:
1) episodes of cataplexy, occurring in at least a few times per mo
a) in individuals with long standing disease, brief (sec to min) episodes of sudden bilateral loss of muscle tone w maintained consciousness that are precipitated by laughter or joking
b) in children or individuals with 6 mo of onset, spontaneous grimaces or jaw opening episodes with tongue thrusting or a global hypotonia, without any obvious emotional triggers
2. hypocretin deficiency less than or equal to one third of values obtained in healthy subjects tested using the same assay, or less than or equal to 110 pg/mL. low CSF levels of hypocretin-1 must not be observed in context of acute brain injury, inflammation, or infection
3. nocturnal sleep polysomnography showing rapid eye movement (REM) sleep latency less than or equal to 15 min or a multiple sleep latency test showing a mean sleep latency less than or equal to 8 min and 2 or more sleep-onset REM periods
tell about metabolism physiological circadian pathways
NAMPT (nicotinamide phosphoribosylatransferase)
->
NAD+ (nicotinamide adenine dinucleate)
-> one of these
fatty acid oxidation
krebs cycle
glycolysis
NADH
= metabolism!
discuss metabolism and liver circadian pathophysiology
- disruption of circadian clock leads to arrhythmic patterns and reduced NAMPT levels, with BMAL1 knockout mice exhibiting decreased NAD+ levels and impaired fatty acid oxidation, diminishing their ability to convert fatty acids into energy
can occur in the liver, where the disruption leads to problems in the rhythmic expression of genes that assist with liver storage and energy production. can lead to inefficient fat oxidation, increased fat accumulation in the liver, and higher risk of conditions like cirrhosis
pancreas physiological circadian pathways
- insulin is secreted in a circadian pattern. your body handles glucose differently depending on the time of day. glucose tolerance goes down at night.
- BMAL 1 within the pancreas has been shown to be very important with proper insulin secretion
- studies show that BMAL1 knockout pancreatic beta cells (black) secrete less insulin compared to normal beta cells (grey)
Type 2 diabetes and circadian pathophysiology
- T2D causes elevated glucose levels
- factors leading to fragmented sleep have shown to increase risk of T2DM
- exposure to nutrients at night lead to higher levels of glucose and triglycerides in the blood
- rats that were fed high fat diets during “night” sessions developed insulin resistance and hepatic steatosis unlike controls
CVS + circadian pathways
- bp and HR peak during the am and gradually decline throughout the day and evening eventually reaching its lowest point at night
- autophagy homeostasis is invaluable to CVS health and autophagic machinery has been known to follow a diurnal pattern
autophagy
recycling of cellular components during cellular stress
what’s increased in the am w circadian rhythm
increased vascular tone
increased blood coagulability
increased o2 demand
increased HR
with increased HR + BP -> increased cell death -> higher incidence of CVS events
with circadian misalignment what happens
- sleep deprivation, poor quality sleep, shift work, high-fat diet (increased insulin resistance, decreased insulin secretion)
- increased sympathetic tone
- increased glucocorticoids
- increased glucose tolerance
- increased orexigenic signaling
- muscle: increased fatty acid uptake, increased glycolytic metabolism
- fat: increased lipogenesis, increased adiponectin production
- liver: increased glycogen synthesis, decreased cholesterol synthesis, increased bile acid synthesis
- pancreas: increased insulin secretion
sleep fasting effects
- muscle: increased oxidative metabolism
- fat: increased lipid catbolism, leptin secretion
- liver: increased gluconeogenesis, glycogenolysis, mitochondrial biogenesis
- pancreas: increased glucagon secretion
advice for better sleep
- getting up/sleeping at consistent times
- naps >20 min disrupt sleep
- avoid phone/tv before bed
- avoid caffeine, alcohol, and nicotine
- dark, quiet, mildly chilly room
- limit large amounts of nutrients right before bed
- exercise during wake periods, avoid before bed
