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Publication : Total abdominal irradiation exposure impairs cognitive function involving miR-34a-5p/BDNF axis.

First Author  Cui M Year  2017
Journal  Biochim Biophys Acta Volume  1863
Issue  9 Pages  2333-2341
PubMed ID  28668331 Mgi Jnum  J:256823
Mgi Id  MGI:6104599 Doi  10.1016/j.bbadis.2017.06.021
Citation  Cui M, et al. (2017) Total abdominal irradiation exposure impairs cognitive function involving miR-34a-5p/BDNF axis. Biochim Biophys Acta 1863(9):2333-2341
abstractText  Radiotherapy is often employed to treat abdominal and pelvic malignancies, but is frequently accompanied by diverse acute and chronic local injuries. It was previously unknown whether abdominal and pelvic radiotherapy impairs distant cognitive dysfunction. In the present study, we demonstrated that total abdominal irradiation (TAI) exposure caused cognitive deficits in mouse models. Mechanically, microarray assay analysis revealed that TAI elevated the expression level of miR-34a-5p in small intestine tissues and peripheral blood (PD), which targeted the 3''UTR of Brain-derived neurotrophic factor (Bdnf) mRNA in hippocampus to mediate cognitive dysfunction. Tail intravenous injection of miR-34a-5p antagomir immediately after TAI exposure rescued TAI-mediated cognitive impairment via blocking the up-regulation of miR-34a-5p in PD, resulting in restoring the Bdnf expression in the hippocampus. More importantly, high throughput sequencing validated that the gut bacterial composition of mice was shifted after TAI exposure, which was retained by miR-34a-5p antagomir injection. Thus, our findings provide new insights into pathogenic mechanism underlying abdominal and pelvic radiotherapy-mediated distant cognitive impairment.
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