Effect of Low-Dose-Rate Radiation on Cognition and Gene Expression Profiles in Type II Diabetes Mellitus Mouse Model

Diabetes, a chronic metabolic disorder that disrupts blood glucose regulation, often results in cognitive impairment, diminishing the quality of life of affected individuals. H owever, the effect of low-dose-rate radiation on the progression of type 2 diabetes mellitus (T2DM) remains largely unexplored. Therefore, this study aimed to investigate whether low-dose-rate radiation could affect diabetic cognitive function and elucidate the underlying mechanisms using a mouse model of T2DM. In this study, male db/db (DB) mice were exposed to low-dose-rate (LDR) radiation, and their locomotor activity and cognitive functions were evaluated using the open-field and object recognition memory tests, respectively. The DB group exhibited diminished activity compared to the C57BL/6 mice used for wild-type (WT) group. Although no significant change was evident in locomotor activity, exposure to 2 Gy attenuated cognitive dysfunction in the DB group, as determined by the object recognition memory test. Following LDR radiation exposure, a total of 32 differentially expressed genes were identified in the hippocampus of DB mice (p < 0.05, fold change > 1.5). Subsequent analyses using DAVID and STRING clustered these genes into pathways related to apoptotic process, transcription, cellular response, cell differentiation, and long-term memory. Real-time polymerase chain reaction analysis indicated that LDR radiation ameliorated the expression of genes, including Arc, Bcl6, Cpne1, Egr1, and Nr4a1 in the hippocampus of DB mice, which was consistent with the RNA-sequencing data. Therefore, this study suggests the potential of LDR radiation to ameliorate cognitive function in DB mice, possibly by regulating genes associated with transcription, neuronal differentiation, and long-term memory in the hippocampus. These findings identify candidate genes for further investigation regarding the role of radiation in the progression of T2DM.