Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Köln
[2021]
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | X, 106 Seiten Illustrationen, Diagramme |
Internformat
MARC
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| 100 | 1 | |a Schilasky, Esther |e Verfasser |0 (DE-588)1240351038 |4 aut | |
| 245 | 1 | 0 | |a Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |c vorgelegt von Esther Schilasky, geb. Engelhardt |
| 246 | 1 | 3 | |a signaling |
| 246 | 1 | 3 | |a kappa B |
| 246 | 1 | 0 | |a signaling |
| 246 | 1 | 0 | |a kappa B |
| 264 | 1 | |a Köln |c [2021] | |
| 300 | |a X, 106 Seiten |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Universität zu Köln |d 2021 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1248172280/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033575656&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-033575656 | ||
Datensatz im Suchindex
| _version_ | 1804183953449418752 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
TABLE
OF
CONTENTS
I.
LIST
OF
FIGURES
......................................................................................................................
IV
II.
LIST
OF
TABLES
.......................................................................................................................
VI
III.
LIST
OF
ABBREVIATIONS
........................................................................................................
VII
IV.
ABSTRACT
................................................................................................................................
IX
V.
ZUSAMMENFASSUNG
..............................................................................................................X
1
INTRODUCTION
...........................................................................................................................
1
1.1
NEUROINFLAMMATION
....................................................................................................................
1
1.2
GLIA
CELLS
.....................................................................................................................................
1
1.2.1
MICROGEA
ORIGIN
AND
THEIR
FUNCTION
IN
CNS
HOMEOSTASIS
.............................................
2
1.2.2
REACTIVE
MICROGEA
AND
THEIR
ROLE
IN
NEUROINFLAMMATION
..............................................
5
1.2.3
ASTROCYTE
MORPHOLOGY
AND
THEIR
HOMEOSTATIC
FUNCTIONS
..............................................
7
1.2.4
REACTIVE
ASTROCYTES
(ASTROGUOSIS)
AND
THEIR
ROLE
IN
NEUROINFLAMMATION
...................
10
1.3
NUCLEAR
FACTOR
KAPPA
B
(NF
K
B)
SIGNALING
IN
THE
CNS
...................................................
12
2
OBJECTIVES
.............................................................................................................................
15
3
RESULTS
...................................................................................................................................
16
3.1
DIFFERENTIAL
ACTIVATION
OF
MICROGEA
AND
ASTROCYTES
AFTER
BRAIN
INJURY
.................................
16
3.2
DIFFERENTIAL
NF
K
B
ACTIVATION
DYNAMICS
IN
MICROGEA
AND
ASTROCYTES
AFTER
BRAIN
INJURY
IN
VIVO
...........................................................................................................................................................
19
3.3
GENERATION
OF
A
MICROGEA-SPECIFIC
NEMO
KNOCK-OUT
MOUSE
ENE
..................................
21
3.4
NEMO
REGULATES
MICROGEA
CELL
NUMBER
AFTER
CORTICAL
SW
INJURY
IN
VIVO
..........................
22
3.5
NEMO
MKO
MICROGEA
KEEP
IN
A
MORE
REACTIVE
STATE
AFTER
CORTICAL
SW
INJURY
.....................
25
3.6
INCREASED
PROEFERATION
AND
CEU
DEATH
IN
NEMO
MK )
MICE
AT
7DPS
.....................................
27
3.7
INCREASED
TISSUE
INFLAMMATION
UPON
MICROGEA-SPECIFIC
NEMO
DEPLETION
AFTER
CORTICAL
SW
INJURY
..............................................................................................................................................
30
3.8
NEMO
REGULATES
MICROGEA
POOL
EXPANSION
AFTER
LASER
LESION
...........................................
31
I
TABLE
OF
CONTENTS
3.9
NEMO
PREVENTS
MICROGLIA
LOSS
BY
NF
K
B
INDEPENDENT
FUNCTIONS
..................................
34
3.10
GENERATION
OF
ASTROCYTE-SPECIFIC
NEMO
KNOCK-OUT
MOUSE
LINE
......................................
35
3.11
ASTROCYTES
DO
NOT
DIE
AND
STILL
BECOME
REACTIVE
UPON
NEMO
DELETION
AFTER
BRAIN
INJURY
........................................................................................................................................
37
3.12
NEMO
AKO
MICROGLIA
ARE
MORE
REACTIVE
AFTER
CORTICAL
SW
INJURY
..........................................
40
3.13
NEMO
DEPLETION
IN
ASTROCYTES
ATTENUATES
NEUROINFLAMMATION
AFTER
CORTICAL
SW
INJURY43
4
DISCUSSION
.............................................................................................................................
45
4.1
MICROGLIA
AND
ASTROCYTES
ACTIVATION
FOLLOWING
CORTICAL
SW
INJURY
......................................
45
4.2
CELL-SPECIFIC
EXPRESSION
OF
P65
DURING
CNS
INJURY
.............................................................
46
4.3
CELL-SPECIFIC
EFFECTS
INDUCED
BY
MICROGLIAL
NEMO
DELETION
.............................................
48
4.3.1
MICROGLIA
VIABILITY
.............................................................................................................
48
4.3.2
MICROGLIA
PHAGOCYTOSIS
AND
PROLIFERATION
.....................................................................
49
4.3.3
GLIAL
REACTIVITY
...................................................................................................................
51
4.4
CELL-SPECIFIC
EFFECTS
INDUCED
BY
ASTROCYTIC
NEMO
DELETION
..............................................
53
4.4.1
ASTROCYTE
VIABILITY
.............................................................................................................
53
4.4.2
GLIAL
REACTIVITY
...................................................................................................................
53
4.5
CONCLUSION
AND
OUTLOOK
..........................................................................................................
55
5
MATERIAL
AND
METHODS
.........................................................................................................
56
5.1
MOUSE
HANDLING
AND
GENETIC
MANIPULATION
...........................................................................
56
5.2
GENOTYPING
................................................................................................................................
56
5.3
TAMOXIFEN
TREATMENT
...............................................................................................................
57
5.4
SURGICAL
PROCEDURES
..................................................................................................................
58
5.4.1
STEREOTACTIC
STAB-WOUND
(SW)
INJURY
AND
VIRAL
INJECTION
............................................
58
5.4.2
CHRONIC
CRANIAL
WINDOW
IMPLANTATION
...........................................................................
58
5.5
IN
VIVO
CHRONIC
2PLSM
IMAGING
..............................................................................................
59
5.6
TRANSCARDIAL
PERFUSION
AND
FLUORESCENCE
IMMUNODETECTION
..............................................
61
5.7
CLICK-IT
EDU
ASSAY
...................................................................................................................
62
II
TABLE
OF
CONTENTS
5.8
TRANSMISSION
ELECTRON
MICROSCOPY
.......................................................................................
62
5.9
ISOLATION
AND
ENRICHMENT
OF
MICROGLIA
.................................................................................
62
5.10
ISOLATION
OF
GLIA
CELLS
VIA
FLUORESCENCE-ACTIVATED
CELL
SORTING
(FACS)
...............................
63
5.11
SDS-PAGE
AND
WESTERN
BLOTTING
...............................................................................................
64
5.12
SP3
BASED
PROTEIN
DIGESTION
...................................................................................................
65
5.13
MASS
SPECTROMETRY
(MS)
.........................................................................................................
66
5.14
BIOINFORMATICS
MS
DATA
ANALYSIS
............................................................................................
67
5.15
QUANTITATIVE
REAL-TIME
PCR
(QRT-PCR)
...............................................................................
67
5.16
ANALYSIS
AND
STATISTICS
..............................................................................................................
68
5.16.1
QUANTITATIVE
ANALYSIS
.......................................................................................................
68
5.16.2
STATISTICS
............................................................................................................................
71
6
SUPPLEMENTS
.........................................................................................................................
72
7
REFERENCES
............................................................................................................................
78
9
EIDESSTATTLICHE
ERKLARUNG
...............................................................................................
1066
III
|
| adam_txt |
TABLE
OF
CONTENTS
TABLE
OF
CONTENTS
I.
LIST
OF
FIGURES
.
IV
II.
LIST
OF
TABLES
.
VI
III.
LIST
OF
ABBREVIATIONS
.
VII
IV.
ABSTRACT
.
IX
V.
ZUSAMMENFASSUNG
.X
1
INTRODUCTION
.
1
1.1
NEUROINFLAMMATION
.
1
1.2
GLIA
CELLS
.
1
1.2.1
MICROGEA
ORIGIN
AND
THEIR
FUNCTION
IN
CNS
HOMEOSTASIS
.
2
1.2.2
REACTIVE
MICROGEA
AND
THEIR
ROLE
IN
NEUROINFLAMMATION
.
5
1.2.3
ASTROCYTE
MORPHOLOGY
AND
THEIR
HOMEOSTATIC
FUNCTIONS
.
7
1.2.4
REACTIVE
ASTROCYTES
(ASTROGUOSIS)
AND
THEIR
ROLE
IN
NEUROINFLAMMATION
.
10
1.3
NUCLEAR
FACTOR
KAPPA
B
(NF
K
B)
SIGNALING
IN
THE
CNS
.
12
2
OBJECTIVES
.
15
3
RESULTS
.
16
3.1
DIFFERENTIAL
ACTIVATION
OF
MICROGEA
AND
ASTROCYTES
AFTER
BRAIN
INJURY
.
16
3.2
DIFFERENTIAL
NF
K
B
ACTIVATION
DYNAMICS
IN
MICROGEA
AND
ASTROCYTES
AFTER
BRAIN
INJURY
IN
VIVO
.
19
3.3
GENERATION
OF
A
MICROGEA-SPECIFIC
NEMO
KNOCK-OUT
MOUSE
ENE
.
21
3.4
NEMO
REGULATES
MICROGEA
CELL
NUMBER
AFTER
CORTICAL
SW
INJURY
IN
VIVO
.
22
3.5
NEMO
MKO
MICROGEA
KEEP
IN
A
MORE
REACTIVE
STATE
AFTER
CORTICAL
SW
INJURY
.
25
3.6
INCREASED
PROEFERATION
AND
CEU
DEATH
IN
NEMO
MK )
MICE
AT
7DPS
.
27
3.7
INCREASED
TISSUE
INFLAMMATION
UPON
MICROGEA-SPECIFIC
NEMO
DEPLETION
AFTER
CORTICAL
SW
INJURY
.
30
3.8
NEMO
REGULATES
MICROGEA
POOL
EXPANSION
AFTER
LASER
LESION
.
31
I
TABLE
OF
CONTENTS
3.9
NEMO
PREVENTS
MICROGLIA
LOSS
BY
NF
K
B
INDEPENDENT
FUNCTIONS
.
34
3.10
GENERATION
OF
ASTROCYTE-SPECIFIC
NEMO
KNOCK-OUT
MOUSE
LINE
.
35
3.11
ASTROCYTES
DO
NOT
DIE
AND
STILL
BECOME
REACTIVE
UPON
NEMO
DELETION
AFTER
BRAIN
INJURY
.
37
3.12
NEMO
AKO
MICROGLIA
ARE
MORE
REACTIVE
AFTER
CORTICAL
SW
INJURY
.
40
3.13
NEMO
DEPLETION
IN
ASTROCYTES
ATTENUATES
NEUROINFLAMMATION
AFTER
CORTICAL
SW
INJURY43
4
DISCUSSION
.
45
4.1
MICROGLIA
AND
ASTROCYTES
ACTIVATION
FOLLOWING
CORTICAL
SW
INJURY
.
45
4.2
CELL-SPECIFIC
EXPRESSION
OF
P65
DURING
CNS
INJURY
.
46
4.3
CELL-SPECIFIC
EFFECTS
INDUCED
BY
MICROGLIAL
NEMO
DELETION
.
48
4.3.1
MICROGLIA
VIABILITY
.
48
4.3.2
MICROGLIA
PHAGOCYTOSIS
AND
PROLIFERATION
.
49
4.3.3
GLIAL
REACTIVITY
.
51
4.4
CELL-SPECIFIC
EFFECTS
INDUCED
BY
ASTROCYTIC
NEMO
DELETION
.
53
4.4.1
ASTROCYTE
VIABILITY
.
53
4.4.2
GLIAL
REACTIVITY
.
53
4.5
CONCLUSION
AND
OUTLOOK
.
55
5
MATERIAL
AND
METHODS
.
56
5.1
MOUSE
HANDLING
AND
GENETIC
MANIPULATION
.
56
5.2
GENOTYPING
.
56
5.3
TAMOXIFEN
TREATMENT
.
57
5.4
SURGICAL
PROCEDURES
.
58
5.4.1
STEREOTACTIC
STAB-WOUND
(SW)
INJURY
AND
VIRAL
INJECTION
.
58
5.4.2
CHRONIC
CRANIAL
WINDOW
IMPLANTATION
.
58
5.5
IN
VIVO
CHRONIC
2PLSM
IMAGING
.
59
5.6
TRANSCARDIAL
PERFUSION
AND
FLUORESCENCE
IMMUNODETECTION
.
61
5.7
CLICK-IT
EDU
ASSAY
.
62
II
TABLE
OF
CONTENTS
5.8
TRANSMISSION
ELECTRON
MICROSCOPY
.
62
5.9
ISOLATION
AND
ENRICHMENT
OF
MICROGLIA
.
62
5.10
ISOLATION
OF
GLIA
CELLS
VIA
FLUORESCENCE-ACTIVATED
CELL
SORTING
(FACS)
.
63
5.11
SDS-PAGE
AND
WESTERN
BLOTTING
.
64
5.12
SP3
BASED
PROTEIN
DIGESTION
.
65
5.13
MASS
SPECTROMETRY
(MS)
.
66
5.14
BIOINFORMATICS
MS
DATA
ANALYSIS
.
67
5.15
QUANTITATIVE
REAL-TIME
PCR
(QRT-PCR)
.
67
5.16
ANALYSIS
AND
STATISTICS
.
68
5.16.1
QUANTITATIVE
ANALYSIS
.
68
5.16.2
STATISTICS
.
71
6
SUPPLEMENTS
.
72
7
REFERENCES
.
78
9
EIDESSTATTLICHE
ERKLARUNG
.
1066
III |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Schilasky, Esther |
| author_GND | (DE-588)1240351038 |
| author_facet | Schilasky, Esther |
| author_role | aut |
| author_sort | Schilasky, Esther |
| author_variant | e s es |
| building | Verbundindex |
| bvnumber | BV048194530 |
| ctrlnum | (OCoLC)1288148149 (DE-599)KXP1779741529 |
| discipline | Biologie |
| discipline_str_mv | Biologie |
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| id | DE-604.BV048194530 |
| illustrated | Illustrated |
| index_date | 2024-07-03T19:45:03Z |
| indexdate | 2024-07-10T09:31:38Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-033575656 |
| oclc_num | 1288148149 |
| open_access_boolean | |
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| owner_facet | DE-355 DE-BY-UBR DE-83 |
| physical | X, 106 Seiten Illustrationen, Diagramme |
| publishDate | 2021 |
| publishDateSearch | 2021 |
| publishDateSort | 2021 |
| record_format | marc |
| spelling | Schilasky, Esther Verfasser (DE-588)1240351038 aut Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury vorgelegt von Esther Schilasky, geb. Engelhardt signaling kappa B Köln [2021] X, 106 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Universität zu Köln 2021 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1248172280/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033575656&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Schilasky, Esther Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |
| subject_GND | (DE-588)4113937-9 |
| title | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |
| title_alt | signaling kappa B |
| title_auth | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |
| title_exact_search | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |
| title_exact_search_txtP | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |
| title_full | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury vorgelegt von Esther Schilasky, geb. Engelhardt |
| title_fullStr | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury vorgelegt von Esther Schilasky, geb. Engelhardt |
| title_full_unstemmed | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury vorgelegt von Esther Schilasky, geb. Engelhardt |
| title_short | Role of NEMO/NF-κB signalling in microglia and astrocytes reacting to brain injury |
| title_sort | role of nemo nf κb signalling in microglia and astrocytes reacting to brain injury |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1248172280/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033575656&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT schilaskyesther roleofnemonfkbsignallinginmicrogliaandastrocytesreactingtobraininjury AT schilaskyesther signaling AT schilaskyesther kappab |
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