Dokument: Chronic Impact of Nanoparticles on Caenorhabditis elegans: Neurodegeneration, Behavioral Impairments, and Molecular Mechanisms
| Titel: | Chronic Impact of Nanoparticles on Caenorhabditis elegans: Neurodegeneration, Behavioral Impairments, and Molecular Mechanisms | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67953 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250106-131958-1 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Le, Dang Tri [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. rer. nat. von Mikecz, Anna [Gutachter] Prof. Dr. Willbold, Dieter [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | The rapid advancement of nanotechnology in recent decades has significantly boosted the production of engineered nanomaterials, which are now utilized in almost every aspect of our daily lives, including agriculture and food production. Engineered nanoparticles increasingly accumulate in natural sinks such as soil and surface waters, prompting questions about their environmental and health impacts. While most current studies focus on the acute effects of nanoparticles, there is a notable gap in research exploring their prolonged nano-bio-interactions. C. elegans serves as a realistic target organism for studying long-term, age-dependent nano-bio-interactions. It is widely used in neurotoxicology, lifespan studies, and the investigation of molecular pathways linked to neurodegeneration. Previous research in C. elegans has shown acute effects of certain nanoparticles on neurodegeneration and neuromuscular defects. However, understanding the temporal connections between nanoparticle-induced neurodegeneration and neuromuscular defects provides valuable insights into age-associated biological effects caused by these NPs. This study shows that silica nanoparticles (NPs) induce neurodegeneration in GABAergic, dopaminergic, and serotonergic neurons of adult hermaphrodite C. elegans. Young and middle-aged worms represent particularly vulnerable age groups. Silica NP effects are characterized by the loss of the anteriormost and posteriormost GABAergic D-type motor neurons. Consequently, C. elegans exposed to silica NPs show a decline in neural behavior, e.g. the organism's ability to move. To investigate the molecular pathways underlying these defects, mass spectrometry-based proteomics was applied. Data analysis reveals a reduction in the prominent gene ontology group associated with the glutamate metabolic process. Since glutamate is a compulsory component for GABA synthesis, the significant downregulation of gdh-1 (Glutamate dehydrogenase) and got-1.2 (Glutamate oxaloacetate transaminase) may play a role in the loss of GABAergic D-type motor neurons following exposure to silica NPs. In order to validate the proteomic data a single-worm tracking (SWT) platform was established for behavioral phenotyping and respective automatic data quantification. As SWT enables automated quantification of thrashing rates and visualization of swimming tracks, the platform proved effective to screen different nanoparticles showing that silica NP components of tire wear (Aerosil 200) significantly reduce C. elegans locomotion. The successful implementation of the SWT now paves the way for phenotype screening of neurotransmission (agonists, antagonists), therapeutic interventions, and, eventually, the interactions of chemical and non-chemical environmental factors, collectively known as the exposome. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie | |||||||
| Dokument erstellt am: | 06.01.2025 | |||||||
| Dateien geändert am: | 06.01.2025 | |||||||
| Promotionsantrag am: | 11.09.2024 | |||||||
| Datum der Promotion: | 22.11.2024 |
