Neuroprotective effects of low-dose ionizing radiation in diabetic rats exposed to chronic unpredictable stress

Objectives: Diabetes mellitus combined with prolonged stress has been linked with neurochemical and functional alterations that may alter brain function. The present study was designed to test the hypothesis that low-dose ionizing radiation (LDIR) may exert neuroprotective effects in diabetic rats exposed to chronic unpredictable stress (CUS) by improving neurochemical and neuroendocrine alterations. Materials and Methods: Diabetes was induced in Wistar rats using streptozotocin (40 mg/kg, intraperitoneally), followed by exposure to CUS and LDIR. Radiation dose (0.1 Gy per session, three times weekly for 15 days) was administered. Behavioral assessments were conducted using open field, rotarod, and object recognition tests. Serum corticosterone levels were measured to evaluate stress-associated neuroendocrine changes. Neurotransmitter levels, including dopamine, serotonin, noradrenaline, and acetylcholine, were quantified in the hippocampus, cerebral cortex, and cerebellum using ELISA. Results: Diabetic rats exposed to CUS showed a significant increase in serum corticosterone levels, reduced neurotransmitter concentrations, and impaired behavioral performance compared with control animals. Treatment with LDIR was associated with significant improvements in corticosterone levels, neurotransmitter concentrations, and behavioral performance compared with untreated diabetic-stressed animals. Combined treatment with LDIR and paroxetine demonstrated additional improvements in selected parameters. Conclusions: These findings demonstrate that LDIR exerts neuroprotective effects in diabetic rats exposed to CUS and suggest its potential as a non-invasive, adjunctive therapeutic approach to mitigate stress-related neuropsychiatric complications associated with diabetes.