Weber, Michaela Bettina Maria (2023). NogoA, a player in neurodegenerative diseases? Characterization of human iPSC-derived NogoA knockout midbrain neurons (Submitted). (Dissertation, Veterinary Pharmacology and Toxicology, Vetsuisse)
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Weber_M_2023_Diss_EN.pdf - Submitted Version Restricted to registered users only Available under License BORIS Standard License. Download (2MB) |
Parkinson's disease (PD) was reported to be the fastest growing neurological disorder worldwide. The histopathological characteristics of PD are a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurite growth inhibitor A (NogoA) was found to co-localize with dopaminergic neurons in the SNpc of the brain. Antagonization of NogoA was shown to increase survival of transplanted human dopaminergic neurons in a PD rat model, suggesting a role of NogoA in PD.
CRISPR/Cas9 technology was used to knockout (KO) the reticulon 4 (RTN4) gene encoding for NogoA. A monoclonal RTN4-KO induced pluripotent stem cell line was successfully generated and differentiated into mature midbrain neurons with a dopaminergic phenotype. The RTN4-KO cell line as well as wild type and mock-transfected control cells were analyzed by immunofluorescence imaging and Western blotting. Markers of neuronal development and synaptic plasticity were not significantly altered between all groups. A visual increase but no significant change of the astrocyte marker S100β was found in the RTN4-KO cells. Furthermore, the RTN4-KO clone showed a significant reduction of α-synuclein and a visual tendency of more dopaminergic neurons. In future studies, the RTN4-KO clone will be used in midbrain organoid models of PD to study the role of NogoA in the pathogenesis and therapy of PD.
Item Type: |
Thesis (Dissertation) |
|---|---|
Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) |
UniBE Contributor: |
Weber, Michaela Bettina Maria |
Subjects: |
600 Technology > 630 Agriculture 500 Science > 570 Life sciences; biology |
Funders: |
[4] Swiss National Science Foundation ; [239] UniBern Forschungsstiftung |
Language: |
English |
Submitter: |
Angélique Ducray |
Date Deposited: |
08 Aug 2023 11:24 |
Last Modified: |
08 Aug 2023 11:24 |
Uncontrolled Keywords: |
NogoA, CRISPR/Cas9, human iPSC-derived midbrain neurons, Parkinson’s disease |
BORIS DOI: |
10.48350/185281 |
URI: |
https://boris.unibe.ch/id/eprint/185281 |
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