RDNA-13. DOSE RESPONSE CURVE FOR RADIATION-INDUCED HYPERSOMNOLENCE (RIH) IN A MOUSE MODEL OF CRANIAL RADIATION: BEHAVIORAL ANALYSIS OF SLEEP AND ACTIVITY

BACKGROUND Radiation therapy is the standard of care for both primary and secondary brain tumors. The majority of patients experience radiation induced hypersomnia (RIH) to varying extents which may impact life quality and treatment tolerance. Previously, we demonstrated that risk is enhanced by presence of select clock gene polymorphisms. The purpose of this study is to establish a mouse model of RIH to test dose effects of cranial irradiation on behavioral sleep and activity prior to introducing tumor in transgenic mice. METHODS Twenty-four non-tumor bearing C57BL/6 mice received whole brain radiation at one of 4 doses (sham, 2Gy, 5Gy, and 15Gy) using a single fraction. Behavior, total activity (distance) and sleep quantity (seconds) were monitored using Phenotyper cages and Ethovision Software with data collected at baseline (10 days) and post-radiation (11 days); percentage of activity was calculated as post-radiation/baseline activity. Blood and tissue samples were collected. RESULTS Baseline activity was not significantly different between groups (F(3.23) = 0.649, p=0.593). Shams and 2Gy mice were not affected by the procedure and activity levels were unchanged, 99.76±1.3% and 103.3±3.5%, respectively. The higher doses, 5Gy and 15Gy, had suppression of general activity compared to baseline with 90.8±2.7% and 88.9±1.3%, respectively. Between the two groups, suppression of activity started after 2 days in 15Gy and 5 days in 5Gy mice. Across three days (8–10), 5Gy and 15Gy (19,872±577sec) had more sleep during their active phase (t=2.27, p=0.03) than sham or 2Gy (17,618±803sec). CONCLUSION Activity and sleep are affected by cranial irradiation in our RIH mouse model in dose dependent manner. This model closely resembles the effects seen in patients and provides a critical tool for interrogating the physiological drivers of RIH. In future studies, we will examine other behaviors and the association between circadian gene variants and RIH susceptibility as previously reported in patients.