Finnerty, Niall J. and O'Riordan, Saidhbhe and Lowry, John P. and Cloutier, Mathieu and Wellstead, Peter
(2013)
Continuous Real-Time in vivo Measurement
of Cerebral Nitric Oxide Supports
Theoretical Predictions of an Irreversible
Switching in Cerebral ROS after Sufficient
Exposure to External Toxins.
Journal of Parkinson’s Disease, 3.
pp. 351-362.
ISSN 1877-7171
Abstract
Background: Mathematical models of the interactions between alphasynuclein (αS) and reactive oxygen species (ROS) predict
a systematic and irreversible switching to damagingly high levels of ROS after sufficient exposure to risk factors associated with
Parkinson’s disease (PD).
Objectives: We tested this prediction by continuously monitoring real-time changes in neurochemical levels over periods of
several days in animals exposed to a toxin known to cause Parkinsonian symptoms.
Methods: Nitric oxide (NO) sensors were implanted in the brains of freely moving rats and the NO levels continuously recorded
while the animals were exposed to paraquat (PQ) injections of various amounts and frequencies.
Results: Long-term, real-time measurement of NO in a cohort of animals showed systematic switching in levels when PQ injections
of sufficient size and frequency were administered. The experimental observations of changes in NO imply a corresponding
switching in endogenous ROS levels and support theoretical predictions of an irreversible change to damagingly high levels of
endogenous ROS when PD risks are sufficiently large.
Conclusions: Our current results only consider one form of PD risk, however, we are sufficiently confident in them to conclude
that: (i) continuous long-term measurement of neurochemical dynamics provide a novel way to measure the temporal change
and system dynamics which determine Parkinsonian damage, and (ii) the bistable feedback switching predicted by mathematical
modelling seems to exist and that a deeper analysis of its characteristics would provide a way of understanding the pathogenic
mechanisms that initiate Parkinsonian cell damage.
| Item Type: |
Article
|
| Additional Information: |
The definitive version of this article is available at DOI: 10.3233/JPD-130198 |
| Keywords: |
Parkinson’s disease; reactive oxygen species; nitric oxide; experimental models; mathematical model; |
| Academic Unit: |
Faculty of Science and Engineering > Chemistry |
| Item ID: |
7009 |
| Identification Number: |
https://doi.org/10.3233/JPD-130198 |
| Depositing User: |
John Lowry
|
| Date Deposited: |
09 Mar 2016 10:29 |
| Journal or Publication Title: |
Journal of Parkinson’s Disease |
| Publisher: |
IOS Press |
| Refereed: |
Yes |
| Funders: |
Science Foundation Ireland (SFI), Enterprise Ireland, Higher Education Authority (HEA) |
| 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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