Son Yeonghoon, Choi Yoonsoo, Jeong Ye Ji, Lee Soo-Ho, Lee Chang Geun, Kim Joong-Sun, Lee Hae-June
Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences (KIRAMS), Seoul, 01812, Republic of Korea.
Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 46033, Republic of Korea.
Mol Neurobiol. 2025 Apr 28. doi: 10.1007/s12035-025-04940-3.
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.
糖尿病是一种破坏血糖调节的慢性代谢紊乱疾病，常常导致认知障碍，降低受影响个体的生活质量。然而，低剂量率辐射对2型糖尿病（T2DM）进展的影响在很大程度上仍未得到探索。因此，本研究旨在调查低剂量率辐射是否会影响糖尿病认知功能，并使用T2DM小鼠模型阐明其潜在机制。在本研究中，雄性db/db（DB）小鼠接受低剂量率（LDR）辐射，并分别使用旷场试验和物体识别记忆试验评估其运动活动和认知功能。与用于野生型（WT）组的C57BL/6小鼠相比，DB组的活动减少。尽管运动活动没有明显变化，但通过物体识别记忆试验确定，2 Gy的辐射剂量减轻了DB组的认知功能障碍。在LDR辐射暴露后，在DB小鼠的海马体中总共鉴定出32个差异表达基因（p < 0.05，变化倍数> 1.5）。随后使用DAVID和STRING进行的分析将这些基因聚类到与凋亡过程、转录、细胞反应、细胞分化和长期记忆相关的途径中。实时聚合酶链反应分析表明，LDR辐射改善了DB小鼠海马体中包括Arc、Bcl6、Cpne1 Egr1和Nr4a1在内的基因表达，这与RNA测序数据一致。因此，本研究表明LDR辐射可能通过调节与海马体中转录、神经元分化和长期记忆相关的基因来改善DB小鼠的认知功能。这些发现确定了候选基因，可进一步研究辐射在T2DM进展中的作用。
