Organophosphate pesticides (OPs) are used globally to control pests on crops and animals. At high exposure levels, several toxic syndromes can occur due to significant acetylcholinesterase (AChE) inhibition. As a result, an acceptable threshold level for human exposure has been established based upon the lack of significant AChE inhibition. However, there has been limited investigation ofthe effects of OP exposure below the acceptable threshold, particularly in adults, despite the many opportunities for long term sub-threshold OP exposure in an occupational setting. The purpose of this thesis was to expand knowledge of the consequences of sub-threshold OP exposure during adulthood on gene expression, behaviour and neurochemistry. Initial studies were performed in adult male rats to develop short term administration models below the threshold for significant AChE inhibition for two commonly used OPs, diazinon and chlorpyrifos. These models were then used to investigate the potential for sub-threshold OP exposure to cause changes in behaviour, neurochemistry and gene expression. Neither OP caused significant changes to working memory, anxiety-like behaviour, locomotor activity and anhedonia (a symptom of depression). However sub-chronic exposure to both OPs caused a marked reduction in marble burying behaviour. Subsequent investigation of diazinon's effects over chronic exposure revealed that marble burying behaviour was affected throughout exposure. Further, diazinon treated rats took longer to bury marbles over sessions, suggesting repetitive/perseverative behaviour may be affected. As for neurochemistry, overall diazinon and chlorpyrifos had no effect on 5-HT levels in the prefrontal cortex, hippocampus, dorsal raphe nucleus and cerebellum. Similarly, overall DA levels in the prefrontal cortex, caudate putamen, hippocampus, substantia nigra and cerebellum were unaffected. However, microarray analysis ofthe hippocampus and dorsal raphe nucleus after chronic diazinon exposure revealed that overall there were changes in genes responsible for synaptic plasticity and synaptic signalling and there may be reorganisation of the synapse. - These data clearly demonstrate that sub-threshold OP exposure alters behaviour and gene expression and suggest a more comprehensive assessment of the risk posed by sub-threshold OP exposure to human health is warranted.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:608355 |
| Date | January 2012 |
| Creators | Savy, Claire Y. |
| Publisher | University of Newcastle Upon Tyne |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.013 seconds