Radiation and CNS effects: summary of evidence from a recent symposium of the Radiation Research Society

This article summarizes a Symposium on 'Radiation risks of the central nervous system' held virtually at the 67th Annual Meeting of the Radiation Research Society, 3-6 October 2021. Repeated low-dose radiation exposure over a certain period could lead to reduced neuronal proliferation, altered neurogenesis, neuroinflammation and various neurological complications, including psychological consequences, necessitating further research in these areas. Four speakers from radiation biology, genetics and epidemiology presented the latest data from their studies seeking insights into this important topic. This symposium highlighted new and important directions for further research on mental health disorders, neurodegenerative conditions and cognitive impairment. Future studies will examine risks of mental and behavioral disorders and neurodegenerative diseases following protracted radiation exposures to better understand risks of occupational exposures as well as provide insights into risks from exposures to galactic cosmic rays. The Million Person Study of Low-Dose Health Effects (MPS) is evaluating the risk of cognitive dysfunction and dementia following intakes of radionuclides and after low-LET external radiation in the workplace. A recent study of Mayak workers in Russia suggested a link with Parkinson's disease following low-LET radiation. High-LET radiation from galactic cosmic ray simulations have reported the potential to accelerate the development of Alzheimer's disease, dementia and anxiety disorders in experimental studies. To date, seven MPS cohorts have evaluated Parkinson's disease at the level of mortality among 515,857 workers and veterans. The excess relative risks (ERR) per 100 mGy dose to brain was estimated for nuclear power plant workers (NPP), industrial radiographers (IR), medical radiation workers (MRW), nuclear weapons test participants and former DOE workers at Mallinckrodt Chemical Works, Mound facility in Ohio, and Los Alamos National Laboratory. There was a general tendency for the risk of Parkinson's disease to increase with increasing estimates of radiation dose to brain. The pooled ERR per 100 mGy for the combined NPP + IR + MRW cohorts was 0.30 (95% CI 0.08, 0.56). Confirmation of these associations are being sought from ongoing studies of an additional 300,000 workers and from linkages within the Centers for Medicare & Medicaid Services (CMS) databases for incidence data on Parkinson's disease for 600,000 workers. Further, a wide range of nonfatal conditions related to dementia and depression are being identified, as are cognitive impairment scores among 600,000 cohort workers alive in 1999 when the CMS data systems became available. Neuroinflammation and synaptic loss have been implicated in cognitive dysfunction seen after brain radiation exposure. Based on evidence that elements of the complement cascade are critical for synaptic pruning by microglia during development and are upregulated in neurodegenerative diseases and aging where synapse density is reduced, we previously demonstrated that deletion of complement receptor 3 (CR3), which is expressed on microglia, protected male mice from dendritic spine loss in the molecular layer of the hippocampus after radiation exposure. Using Thy1-eYFP mice with or without the CR3 receptor, we also found a clear correlation between microglial activation, spine loss and cognitive dysfunction 30 d after 10 Gy cranial irradiation, only in male mice, that is dependent on CR3 expression. Moreover, treatment with leukadherin-1 (LA1), which engages the CR3 receptor, prevents spine loss and cognitive dysfunction due to radiation exposure. To guide application of potential therapeutic interventions, we carried out time course analyses of synaptic density, microglial activation and complement deposition and found that these processes are initiated in the first few days following radiation exposure, suggesting a relatively acute response with long-lasting consequences.

Automated summary

This article summarizes a virtual symposium on the radiation risks of the central nervous system. It discusses the potential neurological complications and psychological consequences of repeated low-dose radiation exposure, emphasizing the need for further research in this area. The symposium highlights new directions for studying mental health disorders, neurodegenerative conditions, and cognitive impairment related to radiation exposure, including occupational exposures and exposures to galactic cosmic rays.