Neuroprotective effects of cytokines in a pesticide model of Parkinson's disease
Public Deposited- Resource Type
- Creator
- Abstract
Substantial evidence suggests an important role for environmental factors in the development of Parkinson's disease (PD). Specifically, numerous studies indicate that agricultural/industrial chemicals, particularly pesticides, can damage dopamine (DA) neurons of the substantia nigra pars compacta, leading to DA deficits and motor impairment. Within the present thesis, we assessed the neurodegenerative and functional effects of the herbicide, paraquat, and determined if its effects would be augmented in the presence of another environmental toxin, namely the fungicide, maneb. To this end PQ + MB did additively provoke neurodegeneration of nigrostriatal DA neurons and motor disturbances, as indicated by reduced open field exploration. Interestingly, however, these behavioral and neurological consequences were observed in mice obtained from Charles River but not identical animals from Jackson laboratories.Given the mounting data suggesting that neuroinflammatory factors mediate neuronal loss in PD, a second component of this study assessed the potential contribution of the cytokines, interleukin-10 (EL-10) and interleukin-6 (IL-6) to paraquat induced neurodegeneration. To this end, mice genetically deficient of IL-6 were greatly resistant to the neurotoxic effects of paraquat. However, central administration of either IL-6 or EL-10 also attenuated the neurodegenerative, as well as the neuroinflammatory (as indicated by diminished microglial density), consequences of both PQ + MB. Thus, EL-6 and IL-10 administration appears to have neuroprotective effects against pesticide toxins. Yet, the fact that inhibition of the cytokine from birth (at least in the case of EL-6) was also neuroprotective, raises the possibility that protective compensatory changes might occur in the absence of the cytokine at developmentally critical times. Taken together, these data further our understanding of how the complex interplay between environmental insult exposure, early life history (e.g. place of breeding) and presence of inflammatory factors (e.g. cytokines) might shape the evolution of PD.
- Subject
- Language
- Publisher
- Thesis Degree Level
- Thesis Degree Name
- Thesis Degree Discipline
- Identifier
- Access Rights
This work is available on request. You can request a copy at https://library.carleton.ca/forms/request-pdf-copy-thesis
- Rights Notes
Copyright © 2009 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
- Date Created
- 2009
Relations
- In Collection: