Vignesh Subramanian ’24

Figure 1: A radiograph captured by X-ray, which produces ionizing radiation, a form of radiation that poses risks of damage to internal tissue.

Ionizing radiation is any radiation traveling in the form of electromagnetic waves or particles with enough energy to knock electrons out of the orbit of atoms. While therapies such as radiotherapy for cancer are intended to emit ionizing radiation in a targeted fashion, it is an undesired side effect of numerous medical imaging procedures, including X-rays and CT scans in diagnostic radiology and gamma rays in nuclear medicine. This can pose significant health risks upon repeated exposure, including cognitive deficits in memory, attentiveness, and spatial processing. However, the extent to which such deficits develop is largely unknown. Previous studies have revealed that the associated health risks also include impaired adult neurogenesis, or a diminished ability to form new neurons as adults.

Researchers led by Dr. Evgeny Amelchenko of Stony Brook University sought to create a new animal model to assess cognitive flexibility, or the ability to shift between behaviors to cope with challenging environments, in mice experiencing radiation-induced cognitive decline. The researchers first irradiated groups of mice with whole-body doses of gamma rays and administered a protein synthesis inhibitor to non-control mice in order to disrupt the function of their hippocampi, a brain structure that memory formation critically depends on. The researchers then developed a hippocampus-dependent behavioral assay, the context discrimination Morris water maze (cdMWM), in which mice must navigate a maze using frequently changing contextual cues. After being trained in MWM tasks, the mice were left to navigate the maze and underwent behavioral observation; their brains were later extracted, stained, and imaged to detect potential structural changes.

The researchers found that while mice exposed to high gamma-ray doses still succeeded in simpler MWM tasks, they demonstrated transient learning and memory deficits when trying to complete the cdMWM tasks. Since the cdMWM tasks required repeated adjustment of search strategies and the recall of previous strategies, this finding suggests that cognitive flexibility was reduced. Furthermore, the mice’s memory deficits resulting from the initial disruption of their hippocampi were not improved over time due to the impairment of the hippocampal neurogenesis. The subsequent immunohistochemical analysis displayed selective activation of newborn neurons when the impaired mice attempted to complete the behavioral tasks, demonstrating that following irradiation, new hippocampal neurons take longer to mature. These findings underscore the potential implications of therapeutic exposure to ionizing radiation for structural integrity and preservation of cognitive function in the brains of humans and other animals.

Works Cited:

[1] E. Amelchenko, et al., Cognitive Flexibility is Selectively Impaired by Radiation and is Associated with Differential Recruitment of Adult-Born Neurons.” Journal of Neuroscience 43, 6061-6083 (2023). doi: 10.1523/JNEUROSCI.0161-22.2023

[2] Image retrieved from: https://commons.wikimedia.org/wiki/File:X-ray_of_the_human_skull_%28side_view%29.jpg