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Total abdominal irradiation exposure impairs cognitive function involving miR-34a-5p/BDNF axis
Ming Cui1, Huiwen Xiao1, Yuan Li1
1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin 300192, China.
Summary
Total abdominal irradiation (TAI) causes cognitive deficits by increasing miR-34a-5p, which suppresses Brain-derived neurotrophic factor (Bdnf). Restoring Bdnf levels via antagomir treatment reversed these radiotherapy-induced cognitive impairments.
Area of Science:
- Oncology
- Neuroscience
- Microbiology
Background:
- Radiotherapy for abdominal/pelvic cancers can cause local injuries.
- The impact of such radiotherapy on distant cognitive function remains unclear.
Purpose of the Study:
- To investigate if total abdominal irradiation (TAI) induces cognitive deficits.
- To elucidate the underlying molecular and microbial mechanisms.
Main Methods:
- Mouse models exposed to total abdominal irradiation (TAI).
- Microarray analysis for gene expression (miR-34a-5p, Bdnf).
- Tail intravenous injection of miR-34a-5p antagomir.
- High-throughput sequencing for gut microbiota analysis.
Main Results:
- TAI exposure led to significant cognitive deficits in mice.
- TAI increased miR-34a-5p expression in tissues and peripheral blood, down-regulating hippocampal Bdnf.
- miR-34a-5p antagomir treatment rescued cognitive impairment and restored Bdnf levels.
- TAI altered gut bacterial composition, an effect mitigated by antagomir treatment.
Conclusions:
- TAI induces distant cognitive impairment through miR-34a-5p mediated suppression of hippocampal Bdnf.
- Gut microbiota dysbiosis is associated with TAI-induced cognitive deficits.
- Targeting miR-34a-5p offers a potential therapeutic strategy for radiotherapy-related cognitive dysfunction.
