Intermittent fasting alleviates irradiation-induced neuronal mitochondrial damage in mice

Area of Science:

• Neuroscience
• Mitochondrial Biology
• Radiotherapy Research

Background:

• Radiation-induced brain injury (RIBI) is a significant clinical challenge following cranial radiotherapy.
• Mitochondrial dysfunction plays a key role in brain aging and neurodegenerative diseases.
• Intermittent fasting (IF) has shown potential in mitigating age-related brain conditions by modulating mitochondrial function.

Purpose of the Study:

• To investigate the protective effects of intermittent fasting (IF) against radiation-induced brain injury (RIBI).
• To assess the impact of IF on mitochondrial function, neurogenesis, neuronal morphology, and cognitive behavior in a mouse model of whole-brain radiotherapy (WBRT).

Main Methods:

• Mice were subjected to whole-brain radiotherapy (WBRT) and treated with intermittent fasting (IF) protocols.
• Mitochondrial ultrastructure and ATP concentrations in the hippocampus were evaluated post-irradiation.
• Neurogenesis (DCX+ cells), neuronal morphology (Golgi staining), and cognitive function (elevated plus-maze test) were assessed.

Main Results:

• IF significantly reduced mitochondrial swelling in hippocampal neurons at both early and late stages post-WBRT.
• ATP concentrations were partially restored in IF-treated mice compared to WBRT-only mice.
• IF promoted neurogenesis and improved neuronal morphology, but cognitive improvements were limited, with shorter open-arm time observed in the elevated plus-maze test.

Conclusions:

• Intermittent fasting demonstrates a neuroprotective effect against radiation-induced brain injury by mitigating mitochondrial damage and enhancing neurogenesis.
• The beneficial effects of IF are more pronounced in the acute phase of RIBI and appear to be time-dependent.
• While IF shows promise in early-stage RIBI, its impact on long-term cognitive function warrants further research.