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Biology 465 > Environmental Light, Circadian Rhythm and Breast Cancer > Flashcards

Environmental Light, Circadian Rhythm and Breast Cancer Flashcards

1
Q

What has occurred to humans now that artificial lighting has been introduced?

A

Humans have spent extended periods of time exposed to artificial light (a new spectral composition), while spending less time being exposed to natural sunlight and darkness we evolved with.

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2
Q

Why is artificial light a problem?

A
  • blue 480nm is needed to make serotonin but inhibits melatonin production
  • 295nm UVB is needed to make Vitamin D
  • artificial light is lacking this wavelength of the broad spectrum noon sun
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3
Q

Why does the wavelength 480nm have to be absent to produce melatonin?

A
  • at this wavelength, seratonin is produced

- it has to be absent because light inhibits the production of melatonin

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4
Q

What are circadian rhythms?

A
  • physical, mental and behavioral changes that follow a roughly 24-hour cycle
  • responds primarily to light and darkness in an organism’s environment
  • usually endogenously generated and self-sustaining
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5
Q

Where are circadian rhythms found?

A

In most living things, such as animals, plants and many tiny microbes

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6
Q

What are the two ways light acts on the body?

A
  • the primary optic tract governs sight and and responses

- the retinohypothalamic tract is most sensitive to blue light stimulation energy in the wavelength of roughly 459-485nm

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7
Q

What is the primary optic tract responsible for?

A
  • visual effects

- visual reflexes

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8
Q

What is the Retinohypothalamic tract responsible for?

A

Acute and longer-term biological/behavioral effects

  • acute effects include melatonin secretion
  • longer-term effects include circadian regulation
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9
Q

What does light signal through?

A

The melanopsin protein
- it undergoes a chemical change when exposed to light received by intrinsically photosensitive retinal ganglion cells in the back of the eye

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10
Q

What are some health effects of the deregulation of the circadian clock?

A
  1. insomnia and sleep disorders
  2. reduced alertness
  3. poor cognitive and motor function
  4. depression, bipolar disorder and seasonal affective disorder
  5. cardio-vascular disease
  6. altered hormone levels
  7. obesity
  8. early-onset diabetes
  9. altered immune function
  10. cancer - breast, prostate and colon
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11
Q

What does the retinohypothalamic tract govern?

A

The circadian, endocrine and neurobehavioural functions

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12
Q

What hormones relate to breast cancer and the hypothalamus exposure to light?

A
  • GnRH
  • Estrogen
  • Progesterone
  • Melatonin
  • Serotonin
  • Vitamin D (Calcitriol)
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13
Q

What is melatonin?

A
  • the darkness hormone
  • secreted only at night (need absence of 480nm light)
  • its precursor is serotonin
  • secreted into the blood by the pineal gland to initiate sleep
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14
Q

Why do melatonin levels vary in a daily cycle?

A

It allows the maintenance of the circadian rhythms of many biological functions

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15
Q

How does the suprachiasmatic nucleaus (SCN) work?

A

It works like a clock.

  • exposure to first light: the clock in SCN begins performing functions like raising body temperature and releasing stimulating hormones like cortisol
  • delays release of hormones such as melatonin until later when darkness arives
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16
Q

What is serotonin?

A

It’s a neurotransmitter that can also function as a hormone

  • highest levels in the afternoon (need 480nm light)
  • derived from tryptophan (constituent of most protein-based foods)
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17
Q

Where is serotonin produced?

A
  • most is produced in the gut, but the remainder is produced in the central nervous system where it functions to regulate mood, appetite, memory and sleep
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18
Q

What is Vitamin D essential for?

A

The formation of normal bones and teeth by maintaining blood levels of calcium and phosphorus but also cell differentiation and development

19
Q

What are some other names for Vitamin D?

A
  • Any of the fat soluble vitamins: D1, D2, D3

- calcitriol = active vitamin D

20
Q

Why is Vitamin not considered a true vitamin but a hormone?

A

We make most of it (~90%) from a metabolite of cholesterol that is present in the skin when exposed to UV light

  • then further processed in the liver and kidneys
  • also can be obtained in our diet (milk products and fatty fish)
21
Q

Where are vitamin D receptors found?

A
  • bone
  • kidney
  • gut
  • immune cells
  • testis
  • breast
22
Q

Why is vitamin D important in cancer?

A

It signals for antiproliferation

23
Q

How is breast cancer and the hormones associated?

A

Breast cancer has been found to be associated with low levels of melatonin, serotonin and vitamin D

24
Q

What environmental changes have been associated with the increased risk of chronic diseases like cancer?

A
  • disruption of biological rhythms (daily, monthly, seasonally) alters hormones
  • the new “built indoor environment”/artificial light which alters the exposure to natural sunlight and darkness
  • geological location and population differences also affect the exposure to light (different latitudes and living in cities/rural areas)
25
Q

What is the exposure to LAN associated with?

A
  • Light at Night (LAN)

- it is correlated with breast and prostate cancer

26
Q

Why is the shift to darkness such a key factor?

A
  • It’s a key factor in the production of melatonin and sleep regulation
  • exposure to light at night diminishes melatonin production
  • since light stimulates serotonin production, altered levels may lead to low levels of melatonin
27
Q

What is the relationship between breast cancer, light and circadian rhythm?

A
  • changes in exposure to light affects biological rhythms, which alters teh metabolism of key hormones (includes GnRH, estrogen, progesterone, testosterone, vitamin D and melatonin)
  • alters neurotransmitters including dopamine and serotonin
  • alters micronutrients including iron
    These changes all increase the risk for chronic disease including breast cancer
28
Q

Summarize the problem with decreased natural daytime light and increased artificial light exposure.

A

Decreased natural daytime light exposure and increased artificial light exposure at night leads to an increased risk of breast cancer

29
Q

What is the rate limiting step in the melatonin biosynthesis in the pineal gland?

A

5HT, serotonin to N-acetylserotonin (NAS)

- the process starts with tryptophan and ends with melatonin (N-acetyl-5-hydroxytryptamine)

30
Q

Are Vitamin D levels also circadian?

A

Yes, like serotonin and body temperature, the serum concentration of vitamin D peaks after mid-day

31
Q

What is the role of Vitamin D?

A
  • regulates calcium absorption

- has important effects on cell longevity and immune functions

32
Q

What are the three essential elements in our biological clocks?

A
  1. A central oscillator that keeps time in the SCN
  2. The ability to sense time cues from the environment and to reset the clock as the seasons change; and varying light cues
  3. A series of outputs tied to distinct phases of the oscillator that regulate activity and physiology
33
Q

Define the period of in Circadian clocks

A

The time to complete one cycle (top of one peak to the next peak)

34
Q

Define the amplitude of rhythm in Circadian clocks

A

One half of the peak-to-trough distance (one wave is 2 amplitudes)

35
Q

What is a phase defined in?

A

Zeitgeber time (ZT)

36
Q

What is Zeitgeber time?

A

Zeitgebers are cues and can be any stimulus that imparts time information to the clock
- have the ability to entrain the clock

37
Q

Where does the central clock reside in mammals?

A

In the suprachiasmatic nucleus (SCN), which is a small region in the hypothalamus of the brain that contains ca. 20000 neurons

38
Q

What are the roles of the SCN?

A
  • produces a rhythmic output that consists of a multitude of neural and hormonal signals that influence sleep and activity
  • signals set the peripheral clocks present in the body
39
Q

How is the SCN clock reset? And what is it sensed by?

A
  • by external light of specific wavelengths

- this is sensed by the ganglion cells of the retinal and carried by the RHT

40
Q

When is the major anabolic period for estrogen?

A

Between 6-9am

41
Q

What does the central clock of the SCN control?

A
  • rest/activity rhythms

- entrained on a daily basis by the dark/light circle

42
Q

When does estrogen and testosterone peak?

A

During the rest period in humans

43
Q

What is the reverse transcript of erythroblastosis gene-alpha (Rec-erb-alpha)?

A

A nuclear receptor oncogene

- first discovered in the 1980s

44
Q

What is the ligand for Rev-erb-alpha? What does the receptor-ligand combination do?

A
  • heme
  • this receptor ligand combination inhibits and fine tunes the clock, allowing the anabolic processes controlled by estrogen and testosterone to move forward

Biology 465 (15 decks)

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