Reid, Caroline H. (2018) Neurochemical Monitoring in a Humanised Murine Model of Parkinson’s Disease using Amperometry and Microdialysis. PhD thesis, National University of Ireland Maynooth.

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Abstract

The main objective of this thesis was to elucidate an overall neurochemical signature of the progression of patient-specific Parkinson’s disease (PD) through the amperometric monitoring of nitric oxide (NO), oxygen (O2) and hydrogen peroxide (H2O2) coupled with microdialysis sampling. The development of a humanised mouse model of PD provides an invaluable tool in which to study PD in a physiological setting. By application of amperometric sensors and microdialysis sampling in these PD models, the functional neurochemical behaviour of the PD can be assessed in vivo. Chapter 1 details an introduction into neurochemical monitoring, PD and the potentially altered role of NO, O2 and H2O2 in contributing to the pathology of this disease. The theory and underlying principles associated with this project are examined in Chapter 2. Chapter 3 includes all of the experimental protocols used throughout the course of this thesis. The validation of each amperometric sensor included in this project is presented in Chapter 4. Previously published performance criteria currently exists on the NO sensor, O2 sensor and H2O2 biosensor. Therefore, it was paramount to ensure their optimum performance prior to application in a murine model. Chapter 5 details the characterisation of the aforementioned sensors in the striatum of NOD SCID mice. Characterisation of each of the amperometric sensors included the systemic and local administration of a variety of inducers and inhibitors of the analyte under investigation. Hence, allowing for the optimal performance of the sensor to be confirmed in vivo. Subsequently, the application of each of these sensors in a humanised model of PD is examined in Chapter 6. Dynamics of NO, O2 and H2O2 levels in the striatum of humanised PINK1, Wild Type (WT) and SHAM mice are included to identify any alterations in the aforementioned analytes that may exist in PD. Additionally, microdialysis sampling conducted in humanised PINK1 and WT mice (Chapter 7) was coupled with amperometric recordings to assess any potential biomarkers of PD. An overall conclusion of this thesis is made in Chapter 8 which aims to deliver a general overview into the main findings obtained throughout this body of work.

Item Type:	Thesis (PhD)
Keywords:	Neurochemical Monitoring; Humanised Murine Model; Parkinson’s Disease; Amperometry; Microdialysis;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	13826
Depositing User:	IR eTheses
Date Deposited:	13 Jan 2021 14:55
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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