Research led by Dr Sarah Marzi (UK DRI at King’s) with collaborators at Imperial College London and the University of Pittsburgh, reveals cells in key brain regions involved in Parkinson’s retain a ‘memory’ of pesticide exposure that disrupts gene expression.
The study found significant changes in the substantia nigra and motor cortex – two areas of the brain known to be affected in Parkinson’s – of rats, following exposure to the pesticide rotenone.
Rotenone is a naturally occurring pesticide known to be toxic to invertebrates and mammals, and is banned in the UK and European Union. In the US and Canada, rotenone is banned for the most part but is still used to control fish populations in lakes and reservoirs. The pesticide is known to cause dysfunction in mitochondria, the cell’s powerhouses, as well as oxidative stress – when molecules are produced that damage the DNA in cells – which the researchers observed across both the brain regions investigated in the study. There is strong epidemiological evidence linking pesticides and Parkinson’s, particularly in the case of farm workers exposed to agricultural pesticides over long periods of time.
In the study, rats were exposed daily to rotenone for a period of 3 weeks, and their brains were analysed after the exposure period. These were compared to rats which had not been exposed to rotenone. The researchers looked for changes in the epigenome of the rats. The epigenome is a collection of chemical markers that act like switches and levers on our DNA, dialling the output of genes up and down in response to our environment.
In the exposed animals, they found that the expression of genes associated with the innate immune system were strongly increased in the substantia nigra, the area of the brain typically associated with Parkinson’s. Investigating further, the team were able to pinpoint that microglia, the brain’s resident immune cells, were activated in the substantia nigra.
Credit: Molly Andrews | UK Dementia Research Institute