Dokument: Destabilisierung von Synapsen durch beta-Amyloid in kultivierten Mausneuronen
| Titel: | Destabilisierung von Synapsen durch beta-Amyloid in kultivierten Mausneuronen | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=33177 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20150212-155734-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Achtzehn, Katharina [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Gottmann, Kurt [Gutachter] Prof. Dr. Müller, Hans Werner [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | Die molekularen Pathomechanismen der Alzheimerschen Demenz (AD) sind nicht vollständig geklärt. Möglicherweise besteht ein Zusammenhang der funktionellen und strukturellen Beeinträchtigungen von Synapsen durch Amyloid β (Aβ) mit einer Störung des neuronalen Zelladhäsionsmoleküls N-Cadherin.
Das Ziel dieser Arbeit war es, diesen Zusammenhang zu untersuchen. Dazu wurden primäre Zellkulturen aus kortikalen Mausneuronen angefertigt. An DIV 9 (days in vitro) wurde ein Medienwechsel mit 7PA2 konditioniertem Medium (KM) vorgenommen, welches zellulär sezernierte Aβ Peptide enthält. Nach mehreren Tagen Inkubation wurden durch immuncytochemische Färbung der dendritische Marker MAP2, Mikrotubuli-assoziiertes Protein, sowie der synaptische Marker VAMP2, vesikelassoziiertes Membranprotein, auch Synaptobrevin (Präsynapse) und das postsynaptische Dichte-Protein PSD95 (Postsynapse) dargestellt. Die quantitative Auswertung der VAMP2 Puncta ergab nach 3 Tagen Inkubation mit 7PA2 KM eine signifikante Abnahme der Dichte der VAMP2 Puncta, nach 4 Tagen zeigte sich zusätzlich eine signifikante Reduktion der Größe der VAMP2 Puncta. Die Gesamtfluoreszenz (Produkt aus Fläche und mittlerer Intensität der Fluoreszenz) der VAMP2 Puncta zeigte nach 3 Tagen eine signifikante Verminderung. Dies war nach 4 Tagen weiterhin als Tendenz, jedoch nicht statistisch signifikant zu beobachten. Die quantitative Auswertung der PSD95 Puncta ergab uneindeutige Effekte, sodass ein unspezifischer Einfluss des 7PA2 KM auf die PSD95 Puncta nicht ausgeschlossen werden konnte. In einem weiteren Versuchsansatz wurde den Zellkulturen zusätzlich zu 7PA2 KM das INP blocking Peptid zugegeben, welches die Funktion des Zelladhäsionsmoleküls N-Cadherin inhibiert. Die quantitative Auswertung der VAMP2 Puncta ergab unter diesen Bedingungen bereits nach 2 Tagen eine signifikante Reduktion sowohl der Dichte als auch der Größe der VAMP2 Puncta. Die quantitative Auswertung der PSD95 Puncta zeigte keine Effekte auf die Dichte und Gesamtfluoreszenz der Puncta. Es zeigte sich nach 2 Tagen eine signifikante Reduktion der Größe der PSD95 Puncta, welche aufgrund der unspezifischen Effekte der Vorversuche ebenfalls als unspezifischer Effekt einzuordnen ist. Die beschriebenen Befunde geben einen starken Hinweis darauf, dass die Blockierung von N-Cadherin vermittelter synaptischer Adhäsion einen beschleunigenden Effekt auf die Synaptotoxizität von Aβ ausübt, was einen neuen Ansatz zur Klärung der synaptischen Pathomechanismen der AD darstellen könnte. | |||||||
| Quelle: | Abe, K; Chisaka, O; Van Roy, F et al. Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat. Neurosci. 2004; 7, 357–363.
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 12.02.2015 | |||||||
| Dateien geändert am: | 12.02.2015 | |||||||
| Promotionsantrag am: | 02.04.2014 | |||||||
| Datum der Promotion: | 15.12.2014 |
