Circulating blood monocytes in amyotrophic lateral sclerosis:
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Ulm
2016
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | 163 Blätter Illustrationen, Diagramme |
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| adam_text | DEPARTMENT OF NEUROLOGY
ULM UNIVERSITY
HEAD: PROF. DR. MED. ALBERT C. LUDOLPH
CIRCULATING BLOOD MONOCYTES IN
AMYOTROPHIC LATERAL SCLEROSIS
DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR
THE DEGREE OF DOCTOR
RERUM NATURALIUM (DR. RER. NAT.) OF THE INTERNATIONAL GRADUATE SCHOOL
IN MOLECULAR
MEDICINE ULM
LISA JOHANNA ZONDLER
BORN IN ESSLINGEN AM NECKAR
2016
TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS
_______________________________________________________________
5
2.
INTRODUCTION________________________________________________________________________
9
2.1 AMYOTROPHIC LATERAL SCLEROSIS (ALS) 10
2.1.1. ALS GENERAL 10
2.1.2. ALS ETIOLOGY, GENETICS AND AFFECTED PATHWAYS 14
2.1.3. ALS PROGRESSION 18
2.1.4. ALS MOUSE MODELS 19
2.1.5. ALS IS A NON-CELL AUTONOMOUS DISEASE 20
2.2. THE IMMUNE SYSTEM 25
2.2.1. CELLS OF THE INNATE IMMUNE SYSTEM 27
2.2.2. CELLS OF THE ADAPTIVE IMMUNE SYSTEM 32
2.2.3. IMPORTANT IMMUNOLOGIC MECHANISMS 32
2.2.4. THE ROLE OF THE IMMUNE SYSTEM IN ALS 36
2.3. AIMS OF THE STUDY 38
3. MATERIALS AND
METHODS_____________________________________________________________39
3.1. MATERIALS 39
3.1.1. HUMAN STUDY COHORT AND STUDY APPROVAL 39
3.1.2. MURINE STUDY COHORT AND STUDY APPROVAL 41
3.1.3. BIOLOGIC MATERIALS 41
3.1.4. MOLECULAR BIOLOGIC MATERIALS 43
3.1.5 KITS AND KIT COMPONENTS 44
3.1.6. CHEMICALS AND REAGENTS 45
3.1.7. BUFFERS 48
3.1.8. ELECTRONIC DEVICES 49
3.1.9. SOFTWARES 49
3.1.10. PLASTIC AND GLASS WARE 49
3.2. METHODS 51
3.2.1. BIOCHEMISTRY 51
3.2.2. CELL CULTURE 53
3.2.3. FLOW CYTOMETRY 61
3.2.4. TRANSCRIPTOMICS 66
3.2.5. IMMUNOHISTOCHEMISTRY
3.2.6. MICROSCOPY 72
3.2.7. ANIMAL ACCOMMODATION 73
3.2.8. STATISTICS 75
4.
RESULTS___________________________________________________________________________
76
4.1. PERIPHERAL MONOCYTES ARE DEREGULATED IN ALS 76
4.1.1. THE SUBTYPE COMPOSITION OF PERIPHERAL MONOCYTES IN ALS PATIENTS
77
4.1.2. PERIPHERAL MONOCYTES ARE DEREGULATED REGARDING THEIR
FUNCTIONALITY IN
ALS 81
4.1.3. ALS MONOCYTES EXHIBIT A DISTINCT GENE EXPRESSION SIGNATURE 88
4.1.4. INVASION OF PERIPHERAL MONOCYTES TO THE CNS IN ALS 93
4.2. MANIPULATION OF ALS MONOCYTES USING HLGG AND FC-FUSION PROTEINS 99
4.2.1. MANIPULATION OF MONOCYTES WITH HLGG AND FC-FUSION PROTEINS
IN VITRO
100
4.2.2. MANIPULATION OF MONOCYTES WITH HLGG AND FC-FUSION PROTEINS
IN VIVO IN
SODLG93A TRANSGENIC MICE 103
5. DISCUSSION________________________________________________ ^
_______________________
114
5.1. THE COMPOSITION OF BLOOD MONOCYTES IS ALTERED IN ALS 114
5.2. PERIPHERAL MONOCYTES ARE FUNCTIONALLY ALTERED IN ALS 117
5.3. IMMUNOMODULATION OF MONOCYTES BY HLGG AND CD95-FC 123
5.4. THE ROLE OF MONOCYTES IN ALS: IMPLICATIONS OF THE PRESENT STUDY TO
THE
CURRENT UNDERSTANDING OF MONOCYTE INVOLVEMENT IN ALS 130
5.5. LIMITATIONS TO THE STUDY AND PROXIMATE QUESTIONS TO ADDRESS 134
6.
CONCLUSIONS______________________________________________________________________
136
7.
SUMMARY_______________________________________________________________________138
8.
BIBLIOGRAPHY____________________________________________________________________
140
9.
APPENDIX_______________________________________________________________________150
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| title | Circulating blood monocytes in amyotrophic lateral sclerosis |
| title_auth | Circulating blood monocytes in amyotrophic lateral sclerosis |
| title_exact_search | Circulating blood monocytes in amyotrophic lateral sclerosis |
| title_full | Circulating blood monocytes in amyotrophic lateral sclerosis Lisa Johanna Zondler |
| title_fullStr | Circulating blood monocytes in amyotrophic lateral sclerosis Lisa Johanna Zondler |
| title_full_unstemmed | Circulating blood monocytes in amyotrophic lateral sclerosis Lisa Johanna Zondler |
| title_short | Circulating blood monocytes in amyotrophic lateral sclerosis |
| title_sort | circulating blood monocytes in amyotrophic lateral sclerosis |
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