Cordycepin, a derivative of nucleoside adenosine, ameliorates neuro-inflammation, neurodegeneration, and cognitive deficits in irradiated mice

Exposure to ionizing radiation in the central nervous system may result in early onset or exacerbated cognitive dysfunction, encompassing various neurodegenerative effects such as reduced neurogenesis, oxidative stress, impaired neuronal structure, and modified brain energy metabolism. The extracellular matrix dysfunction resulting from radiation injury causes inflammation in neurons, which can be observed through elevated levels of pro-inflammatory cytokines such as TNF-α. The molecular and cellular mechanisms that contribute to cognitive decline induced by irradiation remain unresolved. The primary objective of this research is to uncover the precise mechanism underlying the alterations in structure and function of the extracellular matrix, as well as the hastened aging of the brain after exposure to 9 Gray (9Gy) gamma irradiation, and to investigate the potential of cordycepin (CP) in mitigating its detrimental effects. Adult C57BL6 mice received acute head-only irradiation (9 Gy), and were administered CP 20mg/kg, intraperitoneally, once a day for a week. Cohorts of mice were analyzed for cognitive changes using a battery of behavioral tasks after the treatment to characterize learning and memory ability. CP-treated mice showed significantly improved performance on the novel place recognition task and the Morris Water Maze compared with 9Gy-treated mice, suggesting disrupted hippocampal-based memory function. The animal that received 9Gy showed a significant increase in the level of β-Galactosidase compared to CP-treated animals. Our findings indicate that cordycepin may offer protective benefits for the brain in the context of radiation damage and could serve as a therapeutic approach for alleviating mood and memory impairments linked to irradiation. (author)