The impact of mixed radiation and chemicals exposure on neuronal cytotoxicity, ageing and transcription

What is the aim of this project?

The aim of this study is to explore the adverse effects of radiation and chemical exposures on normal human brain functioning. Information relating to the biological response following exposure and possible risk-factors for cognitive impairment, are beginning to emerge. To build on the current body of knowledge this project will use publicly-available large scale next generation sequencing brain datasets to:

  • Identify and study changes in genome sequence, function and activity of brain cells.
  • Improve understanding of the impact of radiation and chemical exposures on the brain, particularly after low-moderate doses.
  • Identify new mutations and genetic biomarkers associated with adverse effect.

Why are we doing this?

As humans, we are continuously exposed to varying levels of radiation and chemical pollutants from the environment, during medical procedures and as a consequence of some occupations. Exposure could possibly mean the increased risk of damage to our cells and primarily our DNA.

In recent years, evidence has been emerging showing ionising radiation as a possible risk-factor for cognitive impairment. Cognitive impairment includes deficits in learning, memory, and information processing ability. For example, higher levels of radiation exposure in adults is associated with reduced cognitive functioning in later life.

At lower doses of radiation, the evidence is more equivocal thus research interest is steadily growing. For instance, some studies show that prenatal exposures may affect brain development and cognitive functioning however there is much more uncertainty about its effects when exposed as on adolescents and adults. This emphasises the necessity of increasing our present understanding on the biological processes and pathways surrounding the adverse effects of radiation on neural cells. For a review on the topic please see Collett et al 2020.

Currently, we are testing our proposed ‘exposure worry’ scales to ensure that it is valid and that it “works”. In order to ensure that our scales work, we need as many test-veterans as possible to take part. This will result in a useful tool to examine the presence and severity of worry in the nuclear test-veteran community. This may also be used to indicate whether or not extra support must be put in place for test-veterans to help overcome their worry.

Why is this study important?

The outcomes of this study will contribute to the growing body of knowledge surrounding exposure to radiation and chemicals as sole agents or as mixtures and their effect on the brain. Our findings should elucidate on biological responses and the adverse pathways that can lead to cognitive impairments. Providing a deeper understanding on potential health risks of such exposures.

What does it involve.

This is a data-driven project. Publicly-available large scale next generation sequencing brain datasets will be analysed using a combination of bioinformatic and statistical tools. In the first instance, genes that are mutated or have a differential expression pattern in radiation exposed subjects compared to healthy individuals will be identified. This will inform on particular biological pathways of interest to explore further.

 

References

Alt, F. and Schwer, B., 2018. DNA double-strand breaks as drivers of neural genomic change, function, and disease. DNA Repair, 71, pp.158-163.

Barazzuol, L., Hopkins, S., Ju, L. and Jeggo, P., 2019. Distinct response of adult neural stem cells to low versus high dose ionising radiation. DNA Repair, 76, pp.70-75.

Collett, G., Craenen, K., Young, W., Gilhooly, M., and Anderson, R.M. (2020) The psychological consequences of (perceived) ionizing radiation exposure: a review on its role in radiation-induced cognitive dysfunction. International Journal of Radiation Biology. Advance online publication. https://doi.org/10.1080/09553002.2020.1793017

Guéguen, Y., Bontemps, A. and Ebrahimian, T., 2018. Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms. Cellular and Molecular Life Sciences, 76(7), pp.1255-1273.

Katsura, M., Cyou-Nakamine, H., Zen, Q., Zen, Y., Nansai, H., Amagasa, S., Kanki, Y., Inoue, T., Kaneki, K., Taguchi, A., Kobayashi, M., Kaji, T., Kodama, T., Miyagawa, K., Wada, Y., Akimitsu, N. and Sone, H., 2016. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells. Scientific Reports, 6(1).

Wei, L., Ding, Y., Liu, Y., Duan, L., Bai, Y., Shi, M. and Chen, L., 2012. Low-Dose Radiation Stimulates Wnt/β-Catenin Signaling, Neural Stem Cell Proliferation and Neurogenesis of the Mouse Hippocampus in vitro and in vivo. Current Alzheimer Research, 9(3), pp.278-289.