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WP4: Animal models


Led by Zenon Sienkiewicz (PHE)
Collaborating institutions: UEF, IT’IS

Background

Previous studies of both animals and humans have provided some evidence that exposure to RF fields may be associated with a number of effects on reproductive health, ageing, behaviour and Alzheimer’s disease. It is still unclear however whether exposure to RF fields may increase cell death and DNA damage in the ageing brain. Very little is currently known about the potential health effects associated with exposure to IF magnetic fields. Animal and cell models allow the possibility of investigating specific associations between exposure to both IF and RF fields and a number of health effects.

Objectives

To investigate mechanisms that may link exposure to RF and IF to behavioural and reproductive effects, as well as cancer, ageing and Alzheimer’s disease (AD) using a series of interlinked animal and cellular models and systems biology. Where appropriate, joint effects with chemical exposures will also be evaluated.

Proposed work

WP4 will carry out a series of interlinked tasks using innovative molecular analyses and behavioural techniques to investigate the effects of long-tern, repeated exposure to IF and RF fields on reproductive health, ageing, behaviour, and on the development of Alzheimer’s disease (AD) in transgenic and wild type mice.

Effects on cognitive function in adult wild type mice will be examined using a sensitive battery of learning and memory tasks; histochemical analysis of the brain will include glial fibrillary acidic protein as a marker for astrocyte activation. Effects on male fertility will be examined by assessing sperm count, as well as daily sperm production, motility and morphology. A behavioural teratology study will also be conducted to determine if there are any functional effects on the developing nervous system:

The effects of exposure to RF fields will be investigated using a transgenic mouse model that shows the hallmarks of accelerated senescence, and immunohistochemistry will be used to characterise any changes in brain structure.  It is also possible that RF fields could affect the development or progression of neurodegenerative diseases, so the effects of exposure will be examined on the neuropathology and behaviour of a transgenic mouse model of AD.  

Lastly, blood and brain cell samples from animals exposed to IF or RF fields will be assayed for evidence of genotoxicity by investigating DNA strand breaks using the Comet assay, and micronuclei with a flow cytometry assay. As the most common form of human glioma arises from astrocytes, assessment of DNA damage in brain samples will be done in isolated astrocytes. Analysis of mini- and microsatellites is a sensitive assay to detect germ line and transgenerational changes: DNA from wild type mice exposed to IR or RF fields will be examined for several microsatellite markers..

For all tasks, numerical dosimetry will be performed to allow exact quantification of absorbed energy in the brain and other organs.  This will be validated using numerical calculations in simplified mice phantoms.

WP4 experimental studies will be performed by PHE and UEF, and IT’IS will provide dosimetry using a number of full anatomical numerical phantoms; Oxford University will contribute expertise on neurodegeneration models.