The involvement of central corticotropin-releasing hormone and its receptors in sleep-wake regulation of mice [Elektronische Ressource] / vorgelegt von Christoph P N Romanowski

Christoph Romanowski

Sujets

• Biologie

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2010
• Nombre de lectures: 10
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

The involvement of central corticotropin-releasing
hormone and its receptors in sleep-wake regulation
of mice

Christoph P N Romanowski





Dissertation
an der Fakultät für Biologie
der Ludwig-Maximilians-Universität München
angefertigt am
Max-Planck-Institut für Psychiatrie in München












The involvement of central corticotropin-releasing
hormone and its receptors in sleep-wake regulation
of mice







Dissertation
an der Fakultät für Biologie
der Ludwig-Maximilians-Universität München


vorgelegt von
Christoph P N Romanowski
aus Augsburg

München 2010




























1. Gutachter: Prof. Dr. Rainer Landgraf
2. Gutachter: Prof. (apl.) Dr. Lutz Wiegrebe

Tag der mündlichen Prüfung: 12. Juli 2010






















Die Arbeit wurde von mir selbstständig und nur unter Verwendung der angegebenen
Hilfsmittel erstellt.

_________________________
(Christoph P N Romanowski)


























Meiner Familie























Table of Contents
Table of Contents

I Abstract .................................................................................................................................................. 1
II Introduction ........................................................................................................................................... 3
2.1 Ways to define sleep ..................................................................................................................... 3
2.1.1 Sleep in invertebrates ............................................................................................................ 3
2.1.2 Sleep in vertebrates ............................................................................................................... 4
2.2 The regulation of sleep and wakefulness in mammals ................................................................. 7
2.2.1 The two process model .......................................................................................................... 7
2.2.1.1 Homeostatic control of sleep (Process S) ...................................................................... 7
2.2.1.2 Circadian control of sleep (Process C) ........................................................................... 8
2.2.2 Neuronal sleep-wake regulation in mammals ...................................................................... 10
2.2.2.1 Wake regulation ............................................................................................................ 10
2.2.2.2 Non-rapid eye movement sleep regulation .................................................................. 12
2.2.2.3 Rapid eye movement sleep regulation ......................................................................... 13
2.2.3 Humoral sleep-wake regulation in mammals ....................................................................... 15
2.3 The hypothalamo-pituitary-adrenocortical axis 17
2.4 The corticotropin-releasing hormone (CRH) ............................................................................... 20
2.4.1 The CRH peptide family ....................................................................................................... 20
2.4.2 The distribution of CRH ....................................................................................................... 20
2.4.3 Stress-related effects of CRH .............................................................................................. 22
2.4.4 Sleep-wake regulatory effects of CRH ................................................................................ 23
2.5 The corticotropin-releasing hormone receptor system ............................................................... 25
2.5.1 The CRH receptor family .... 25
2.5.2 The distribution of the CRH receptors ................................................................................. 27
2.5.3 The stress-related function of the CRH receptors ............................................................... 29
2.5.4 The functional role of the CRH receptors in sleep-wake regulation .................................... 30
2.6 Aim of the thesis .......................................................................................................................... 31
III Materials and Methods ...................................................................................................................... 32
3.1 Experimental animals .................................................................................................................. 32
3.2 Animal housing ............................................................................................................................ 33
3.3 Surgery ........................................................................................................................................ 33
3.4 EEG/EMG recordings .................................................................................................................. 35
3.5 Experimental procedures for testing CRH and ASV-30 .............................................................. 36
3.6 Automated sleep deprivation ....................................................................................................... 38
3.7 Slow wave activity ....................................................................................................................... 40
3.8 Sleep architecture ........................................................................................................
3.9 Analysis of plasma corticosterone levels .................................................................................... 41
3.10 Statistical analysis ..................................................................................................................... 42
IV Results .............................................................................................................................................. 43 Table of Contents
4.1 Sleep and wake responses to CRH injections ............................................................................ 43
4.1.1 C57BL/6J ............................................................................................................................. 43
4.1.2 CRH-R1 CKO and CL .......................................................................................................... 46
4.1.3 CRH-R2 KO and CL ............................................................................................................ 49
4.2 Plasma CORT level changes after CRH injection in CRH-R1 CKO and CL .............................. 53
4.3 Sleep and wake responses in CRH-R1 CKO and CL to CRH injections with ASV-30 treatment ...
......................................................................................................................................................... 54
4.4 CRH-induced changes in sleep architecture ............................................................................... 58
4.4.1 C57BL/............. 58
4.4.2 CRH-R1 CKO and ... 60
4.4.3 CRH-R2 KO and CL ............................................................................................................ 62
4.4.4 Comparison of sleep architecture between the mouse lines ............................................... 64
4.5 Automated sleep deprivation-induced changes in sleep-wake profiles ...................................... 68
4.5.1 C57BL/6J ............................................................................................................................. 68
4.5.2 CRH-R1 CKO and CL .......................................................................................................... 71
4.5.3 CRH-R2 KO and .... 75
4.6 Accumulation of slow wave activity in response to automated sleep deprivation ....................... 78
4.6.1 C57BL/............. 78
4.6.2 CRH-R1 CKO and ... 80
4.6.3 CRH-R2 KO and CL ............................................................................................................ 82
4.7 Plasma CORT level changes in response to automated sleep deprivation ................................ 84
V Discussion .......................................................................................................................................... 88
5.1 Central CRH-R1 mediates effects of CRH on sleep-wake regulation ......................................... 88
5.1.1 Genetic background might influence baseline slee