The Development of Circadian Rhythms in Human Infants

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Summary 1. Melatonin is produced by the pineal gland. 2. It has an important role in determining day and night rhythms in human physiology. 3. Its synthesis is mainly determined by light/dark cycles. 4. Peak melatonin production is during the night time period with a fall during the day. 5. The age when the melatonin rhythm is thought to stabilise is approximately 3 months of age. 24
1.7 Cortisol Cortisol is a hormone, secreted by the adrenal glands, which has been shown to exhibit one of the most robust circadian rhythms. It is produced in antiphase to melatonin. The role it plays in the „clock‟ and circadian rhythmicity is an emerging and exciting area of research. It has traditionally been a „cross over‟ measure quoted frequently in psychosocial and biological work as a physical measure of „stress.‟ In molecular biology work is has been found to synchronise the clock (see introduction section 1.9.6). It was included as a measure of interest in this study as it may be the „key‟ that unlocks the door to physiological maturation. We do not know the precise role it plays in chronobiology and the consequence of early or late maturation of the corticosteroid axis/rhythm; therefore it is worth exploring. 1.7.1 Production and Regulation of Cortisol Secretion Cortisol is a hormone which is essential for life. It accounts for 95% of glucocorticoid activity. It has a major role in the body‟s ability to process and metabolise glucose, protein and fats. It also facilitates the body‟s normal response to stress. In its absence, a minor illness can cause death. Cortisol is made from cholesterol. It is produced in the adrenal cortex. Cholesterol is acted upon by the enzyme cholesterol desmolase and as a result pregnenolone is made. This is then converted to 17-hydroxypregnenolone; then to 17- hydroxyprogesterone; onto 17-deoxycortisol and finally to cortisol. 25
Page 1 and 2: The Development of Circadian Rhythm
Page 3 and 4: Table of Contents LIST OF FIGURES .
Page 5 and 6: 7.1 Analysis of infant sleep measur
Page 7 and 8: List of Figures Figure 1.1 - Diagra
Page 9 and 10: List of Tables Table 3.1 - Descript
Page 11 and 12: 1 Introduction Happiness is not a m
Page 13 and 14: Each of these independently is impo
Page 15 and 16: There is general agreement, that al
Page 17 and 18: Summary 1. Development encompasses
Page 19 and 20: Figure 1.1 - Diagram illustrating c
Page 21 and 22: A phase shift is used to describe a
Page 23 and 24: 1.4 Ontogeny in Human Infants Well
Page 25 and 26: 1.5.2 Circadian Rhythms in Temperat
Page 27 and 28: 1.5.4 Factors affecting Temperature
Page 29 and 30: 1.6 Melatonin (Reviewed in Cardinal
Page 31 and 32: mechanism by which this occurs is n
Page 33: It is at this time that infant slee
Page 37 and 38: 1.7.3 Circadian pattern of Cortisol
Page 39 and 40: In a separate study, Weerth et al u
Page 41 and 42: Summary 1. Cortisol is crucial to a
Page 43 and 44: NREM sleep has 4 stages. It occupie
Page 45 and 46: 1.8.1 Functions of Sleep The functi
Page 47 and 48: 1.8.3 Ontogeny of Sleep in Infants
Page 49 and 50: Sleep can clearly be used as marker
Page 51 and 52: For the purpose of this study, the
Page 53 and 54: Summary 1. Sleep is defined by lack
Page 55 and 56: Overall the SCN generates signals (
Page 57 and 58: Figure 1.2 - The mammalian circadia
Page 59 and 60: 1.9.3 Molecular Components of the C
Page 61 and 62: Figure 1.3 - Mechanisms from SCN to
Page 63 and 64: 1.9.7 Melatonin and Clock Melatonin
Page 65 and 66: The links between the central clock
Page 67 and 68: Chapter 2 Methods
Page 69 and 70: There were strict inclusion and exc
Page 71 and 72: This personal contact on the postna
Page 73 and 74: 2.1.3 Home monitoring visits The fi
Page 75 and 76: 2.1.4 Further monitoring informatio
Page 77 and 78: Core body temperature was taken sim
Page 79 and 80: 2.3 Collection of urine samples Pai
Page 81 and 82: were read against air at 429 nm aft
Page 83 and 84: allowed the display and comprehensi
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2.8.1 RNA preparation and cDNA synt
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In total three methods were trialle
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2.11 Statistical methods For compar
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test that each infant‟s height an
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Power calculation Sample size: Fift
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3 Results 3.1 Recruited subjects an
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predominantly affluent areas of the
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Birth history and past medical hist
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3.1.3 Socioeconomic demographics of
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her best friend losing her battle w
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Sleep environment of infants All mo
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Summary 1. This study had higher ra
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4 Results 4.1 Core body temperature
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Degrees Celsius 36.70 36.60 36.50 3
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11-13 weeks There is no significant
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Core body temperature (degrees Cels
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Number of infants 10 8 6 4 2 0 7 8
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Mean minimum rectal temperature in
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Mean minimum rectal temperature in
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Figure 4.7 shows the changes in the
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Chapter 5 Result
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4 or 6 hourly samples. Circadian rh
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Figure 5.1 - Distribution of mean n
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5.1.2 Emergence of diurnal rhythm f
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Figure 5.3 - Histogram showing dist
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Figure 5.4 - Changes in night time
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Night-day difference in melatonin s
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Summary 1. There is an increase in
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6 Results DESCRIPTION OF THE URINAR
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Page 145 and 146:
6.1.2 Emergence of diurnal rhythm f
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Figure 6.3 - Histogram showing dist
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Page 151 and 152:
Cortisol values were corrected to a
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6.1.4 Relationship between night an
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Chapter 7 Results
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Mean Length of Sleep/ Wake Bouts Th
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Sleep parameters were recorded as m
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7.3 Development of infant sleep rel
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Figure 7.2 - Changes in infant slee
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Figure 7.4 - Changes in percentage
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Figure 7.5 - Changes in infant frag
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Figure 7.7 - Changes in number of m
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Figure 7.9 - Changes in the percent
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Sleep efficiency (%) 100.0 90.0 80.
Page 175 and 176:
Chapter 8 Results
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Considering only those weeks of mea
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8.2 Description of peripheral gene
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18:30 hours 0.9927; 01:00 ours 1.01
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The weeks after temperature maturat
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Further peripheral gene graphical r
Page 187 and 188:
Raw data points are represented by
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H3f3b/Gap H3f3b/Gap H3f3b/Gap H3f3b
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8.3 Detailed gene expression analys
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Summary 1. H3f3b was selected as ge
Page 195 and 196:
9 Results FACTORS AFFECTING SLEEP A
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Care and infant related factors �
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Table 9.3 - Effect of family occupa
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* Class 7 used as reference group
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Table 9.6 - Effect of measured infa
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Summary: 1. A mature physiological
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10 Results 10.1 Circadian rhythms -
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value of above 0.5 for R squared wa
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Table 10.1 - Temporal relationship
Page 213 and 214:
Chapter 11 Discussion
Page 215 and 216:
� What if any are the factors whi
Page 217 and 218:
11.1 Physiological development - ag
Page 219 and 220:
There are other proven factors whic
Page 221 and 222:
drawbacks of the spread of data - a
Page 223 and 224:
presented in table 6.1 do not have
Page 225 and 226:
separate methods were applied to th
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significant. Sleep latency was cons
Page 229 and 230:
The function of sleep in developmen
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Melatonin secretion was higher on n
Page 233 and 234:
In this study sleeping in the same
Page 235 and 236:
Timing of sleep maturation was diff
Page 237 and 238:
systematic, ordered developmental p
Page 239 and 240:
individual gene plots that provide
Page 241 and 242:
temperature recording devices adapt
Page 243 and 244:
Both melatonin and cortisol rhythms
Page 245 and 246:
Extension of this period of monitor
Page 247 and 248:
Second, we demonstrated the gene of
Page 249 and 250:
Cortisol and melatonin Slope based
Page 251 and 252:
Summary and Future work This study
Page 253 and 254:
� Maximise technique for measurin
Page 255 and 256:
“There is a science of infant car
Page 257 and 258:
References
Page 259 and 260:
Bajanowski, T., Vege, Å., Byard, R
Page 261 and 262:
Chamley, C.A., Carson P, Randall D,
Page 263 and 264:
Frank, M.G., Heller, H.C., 2003. Th
Page 265 and 266:
intrahypothalamic administration of
Page 267 and 268:
Mirmiran, M. & Ariagno, R.L., 2000.
Page 269 and 270:
Rawson, D., Petersen, S.A., Wailoo,
Page 271 and 272:
Stokkan, K.A., Yamazaki, S., Tei, H
Page 273 and 274:
Winter, J.S.D., 1985. The adrenal c
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The Development of Circadian Rhythms in Human Infants

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