Selective neurodegeneration during Parkinson's disease: impact of mitochondrial impairment and cell type-specific properties
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Köln
2018
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | X, 83 Seiten Illustrationen 21 cm |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV045144901 | ||
| 003 | DE-604 | ||
| 005 | 00000000000000.0 | ||
| 007 | t | ||
| 008 | 180823s2018 gw a||| m||| 00||| eng d | ||
| 015 | |a 18,H05 |2 dnb | ||
| 016 | 7 | |a 1155026403 |2 DE-101 | |
| 020 | |c Broschur | ||
| 035 | |a (OCoLC)1136357166 | ||
| 035 | |a (DE-599)DNB1155026403 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c XA-DE | ||
| 049 | |a DE-355 | ||
| 084 | |a 610 |2 sdnb | ||
| 100 | 1 | |a Ricke, Konrad Maximilian |d 1985- |e Verfasser |0 (DE-588)1151650102 |4 aut | |
| 245 | 1 | 0 | |a Selective neurodegeneration during Parkinson's disease |b impact of mitochondrial impairment and cell type-specific properties |c vorgelegt von Konrad Maximilian Ricke |
| 264 | 1 | |a Köln |c 2018 | |
| 300 | |a X, 83 Seiten |b Illustrationen |c 21 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Universität zu Köln |d 2017 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u http://d-nb.info/1155026403/04 |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=030534679&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-030534679 | ||
Datensatz im Suchindex
| _version_ | 1804178812214181888 |
|---|---|
| adam_text | INDEX OF CONTENTS
1 INTRODUCTION______________________________________________________ 1
1.1 AGEING: THE MAIN RISK FACTOR TO DEVELOP PARKINSON*S DISEASE 1
1.2 THE MITOCHONDRIAL NETWORK AND THE MITOCHONDRIAL RESPIRATORY CHAIN 2
1.2.1 MITOCHONDRIAL DNA: STRUCTURE, TRANSCRIPTION AND REPLICATION 3
1.2.2 THE MITOCHONDRIAL RESPIRATORY CHAIN PRODUCES REACTIVE OXYGEN
SPECIES 5
1.2.3 MITOCHONDRIAL DNA DELETIONS AND PARKINSON*S DISEASE 7
1.2.4 MITOCHONDRIAL QUALITY CONTROL AND PARKINSON*S DISEASE 8
1.2.5 OXIDATIVE STRESS AND PARKINSON*S DISEASE 8
1.3 THE DOPAMINERGIC SYSTEM AND THE ELECTRICAL ACTIVITY OF DOPAMINERGIC
NEURONS 9
1.3.1 THE FUNCTIONAL CONNECTION OF DOPAMINERGIC NEURONS IN THE BASAL
GANGLIA NETWORK 10
1.3.2 CALCIUM DYNAMICS AND THE INTRINSIC GENERATION OF ACTION POTENTIALS
IN DA-NS 11
1.3.3 MITOCHONDRIAL CALCIUM SEQUESTRATION 13
1.3.4 DIFFERENTIAL NEURODEGENERATION IN PARKINSON*S DISEASE 14
1.4 OBJECTIVES OF THE STUDY 19
2 METHODS___________________________________________________________20
2.1 CHEMICALS 20
2.2 MOUSE PROCEDURES 21
2.2.1 GENOTYPING 21
2.2.2 ANAESTHESIA 22
2.2.3 IN VIVO TREATMENT WITH ISRADIPINE BY OSMOTIC PUMPS 22
2.2.4 ISRADIPINE PLASMA CONCENTRATION 23
2.2.5 SPONTANEOUS MOTOR ACTIVITY 23
2.3 HISTOLOGY 24
2.3.1 TISSUE PREPARATION FOR CRYOSECTIONING 24
2.3.2 COX-SDH STAINING 24
2.3.3 INTRACARDIAC PERFUSION AND TISSUE PREPARATION FOR PARAFFIN
SECTIONS 25
2.3.4 IMMUNOHISTOCHEMISTRY 25
2.3.5 NUCLEAR COUNTERSTAINING 26
2.3.6 MICROSCOPY 28
2.3.7 QUANTIFICATION OF IMMUNOHISTOCHEMICAL STAININGS 28
2.3.8 DOPAMINERGIC STRIATAL FIBRE DENSITY 28
2.3.9 STEREOLOGICAL QUANTIFICATION OF DOPAMINERGIC NEURON NUMBER 29
2.3.10 TYROSINE HYDROXYLASE-CALBINDIN-D28K-COLOCALIZATION 30
2.4 ACUTE MIDBRAIN SECTION RECORDINGS 30
2.4.1 SECTION PREPARATION FOR OXYGEN CONSUMPTION MEASUREMENTS AND
MITO-ROGFP
IMAGING 30
2.4.2 OXYGEN CONSUMPTION MEASUREMENTS OF MIDBRAIN SECTIONS 31
2.4.3 MULTIPHOTON MICROSCOPY OF THE REDOX-SENSITIVE GFP IN THE
MITOCHONDRIAL MATRIX OF
DOPAMINERGIC NEURONS 32
2.5 STATISTICS 35
3 RESULTS
___________________________________________________________
36
3.1 THE PARKINSON*S DISEASE PHENOTYPE OF MITOPARK MICE IS NOT ALTERED BY
IN VIVO
TREATMENT WITH AN INHIBITOR FOR THE VOLTAGE-GATED CALCIUM CHANNEL 1.3 36
3.1.1 MITOPARK MICE SHOW A PROGRESSIVE BEHAVIOURAL PD PHENOTYPE 36
3.1.2 THE PROGRESSIVE MOTOR IMPAIRMENT OF MITOPARK MICE IS ACCOMPANIED
BY THE
DEGENERATION OF DOPAMINERGIC STRIATAL PROJECTIONS 37
3.1.3 TREATMENT OF MITOPARK MICE WITH ISRADIPINE DOES NOT SLOW DOWN THE
PROGRESSION OF
THE PD PHENOTYPE 38
3.2 THE SELECTIVE VULNERABILITY OF MIDBRAIN DOPAMINERGIC NEURONS OF
MITOPARK MICE:
INFLUENCE OF CALBINDIN? 40
3.2.1 CYTOCHROME C OXIDASE-DEFICIENCY PRECEDES THE DEGENERATION OF
DOPAMINERGIC
NEURONS IN MITOPARK MICE 40
3.2.2 A LARGE FRACTION OF SURVIVING DOPAMINERGIC NEURONS IN MITOPARK
MICE EXPRESS
CALBINDIN-D28K 42
3.3 THE MITOCHONDRIAL REDOX-RATIO OF MIDBRAIN DOPAMINERGIC NEURONS 44
3.3.1 EXPRESSION OF MITO-ROGFP IN DOPAMINERGIC NEURONS NEITHER LEADS TO
MITOCHONDRIAL
DYSFUNCTION NOR INDUCES THE LOSS OF STRIATAL DOPAMINERGIC PROJECTIONS 44
3.3.2 OXIDIZING AND REDUCING AGENTS INDUCE SIMILAR VARIATIONS IN THE
FLUORESCENCE
INTENSITY OF MITO-ROGFP IN BOTH DOPAMINERGIC MIDBRAIN REGIONS 45
3.3.3 KINETICS OF MITO-ROGFP SIGNALS AND ANALYSIS OF THE REDOX-RATIO OF
THE
MITOCHONDRIAL NETWORK IN DOPAMINERGIC NEURONS 46
3.3.4 INHIBITION OF MITOCHONDRIAL COMPLEX IV INCREASES THE REDOX-RATIO
OF SNC DA-NS 49
3.3.5 MITOPARK MICE DISPLAY AN INCREASED MITOCHONDRIAL REDOX-RATIO IN
SNC DA-NS,
WHICH CAN BE LOWERED BY INHIBITING NEURONAL AS WELL AS MITOCHONDRIAL
CALCIUM INFLUX
51
4
4.1
DISCUSSION
4.3
4.4
ISRADIPINE DOES NOT SLOW DOWN THE DEVELOPMENT OF THE PD PHENOTYPE OF
MITOPARK
MICE 54
MIDBRAIN DOPAMINERGIC NEURON POPULATIONS OF MITOPARK MICE DISPLAY
DIFFERENTIAL
VULNERABILITY 56
CALBINDIN AFFECTS THE DEGENERATION OF DOPAMINERGIC NEURONS 58
THE MITOCHONDRIAL REDOX-RATIO IS ELEVATED BY INHIBITION OF MITOCHONDRIAL
COMPLEX
IV 59
INHIBITION OF NEURONAL AND MITOCHONDRIAL CALCIUM INFLUX DECREASES THE
REDOX-RATIO
OF VULNERABLE SNC DA-NS IN MITOPARK MICE 61
CONCLUSIONS
64
REFERENCES 65
ANNEXE 80
7.1
7.2
SUPPLEMENTARY INFORMATION FOR METHODS
SUPPLEMENTARY FIGURES FOR RESULTS
80
82
|
| any_adam_object | 1 |
| author | Ricke, Konrad Maximilian 1985- |
| author_GND | (DE-588)1151650102 |
| author_facet | Ricke, Konrad Maximilian 1985- |
| author_role | aut |
| author_sort | Ricke, Konrad Maximilian 1985- |
| author_variant | k m r km kmr |
| building | Verbundindex |
| bvnumber | BV045144901 |
| ctrlnum | (OCoLC)1136357166 (DE-599)DNB1155026403 |
| discipline | Medizin |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01403nam a2200349 c 4500</leader><controlfield tag="001">BV045144901</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">180823s2018 gw a||| m||| 00||| eng d</controlfield><datafield tag="015" ind1=" " ind2=" "><subfield code="a">18,H05</subfield><subfield code="2">dnb</subfield></datafield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">1155026403</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="c">Broschur</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1136357166</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DNB1155026403</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">XA-DE</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-355</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">610</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Ricke, Konrad Maximilian</subfield><subfield code="d">1985-</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1151650102</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Selective neurodegeneration during Parkinson's disease</subfield><subfield code="b">impact of mitochondrial impairment and cell type-specific properties</subfield><subfield code="c">vorgelegt von Konrad Maximilian Ricke</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Köln</subfield><subfield code="c">2018</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">X, 83 Seiten</subfield><subfield code="b">Illustrationen</subfield><subfield code="c">21 cm</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="b">Dissertation</subfield><subfield code="c">Universität zu Köln</subfield><subfield code="d">2017</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">B:DE-101</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://d-nb.info/1155026403/04</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030534679&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-030534679</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV045144901 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T08:09:55Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-030534679 |
| oclc_num | 1136357166 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | X, 83 Seiten Illustrationen 21 cm |
| publishDate | 2018 |
| publishDateSearch | 2018 |
| publishDateSort | 2018 |
| record_format | marc |
| spelling | Ricke, Konrad Maximilian 1985- Verfasser (DE-588)1151650102 aut Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties vorgelegt von Konrad Maximilian Ricke Köln 2018 X, 83 Seiten Illustrationen 21 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Universität zu Köln 2017 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1155026403/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030534679&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Ricke, Konrad Maximilian 1985- Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties |
| subject_GND | (DE-588)4113937-9 |
| title | Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties |
| title_auth | Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties |
| title_exact_search | Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties |
| title_full | Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties vorgelegt von Konrad Maximilian Ricke |
| title_fullStr | Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties vorgelegt von Konrad Maximilian Ricke |
| title_full_unstemmed | Selective neurodegeneration during Parkinson's disease impact of mitochondrial impairment and cell type-specific properties vorgelegt von Konrad Maximilian Ricke |
| title_short | Selective neurodegeneration during Parkinson's disease |
| title_sort | selective neurodegeneration during parkinson s disease impact of mitochondrial impairment and cell type specific properties |
| title_sub | impact of mitochondrial impairment and cell type-specific properties |
| topic_facet | Hochschulschrift |
| url | http://d-nb.info/1155026403/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030534679&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT rickekonradmaximilian selectiveneurodegenerationduringparkinsonsdiseaseimpactofmitochondrialimpairmentandcelltypespecificproperties |
Es ist kein Print-Exemplar vorhanden.
Inhaltsverzeichnis