Forced Running Exercise Mitigates Radiation-Induced Cognitive Deficits Via Regulated DNA Hydroxymethylation

Abstract

Aim: Roles of forced running exercise (FE) in remediation of neurogenesis inhibition and radiation-induced cognitive dysfunction were investigated in a whole-brain irradiation mice model via the regulation of DNA 5-hydroxymethylation modification (5 hmC) and its catalytic enzymes ten–eleven translocation (Tet) proteins. Materials & methods: Hippocampal neurogenesis and cognitive function, DNA 5 hmC level and Tet expression were determined in mice. Results: The expression of DNA 5 hmC and Tet2, brain-derived neurotrophic factor significantly decreased in hippocampus postradiation. FE mitigated radiation-induced neurogenesis deficits and cognitive dysfunction. Furthermore, FE increased 5 hmC and brain-derived neurotrophic factor expression. SC1, a Tet inhibitor, reversed partly such changes. Conclusion: Tet-mediated 5 hmC modification represents a kind of diagnostic biomarkers of radiation-induced cognitive dysfunction. Targeting Tet-related epigenetic modification may be a novel therapeutic strategy for radiation-induced brain injury.

Keywords::

• 5-hydroxymethylcytosine
• BDNF
• forced running exercise
• neurogenesis
• radiation-induced cognitive dysfunction
• ten–eleven translocation enzyme

Financial & competing interests disclosure

This study was supported by the National Key R&D Program of China (2017YFE0103700); the National Natural Science Foundation of China Grants 81172128 (Y Tian), 81372411 (Y Tian); the Jiangsu Provincial Special Program of Clinical Medical Science (BL2014040); Project of Jiangsu Natural Science Foundation (BK20171224); Suzhou Cancer Clinical Medical Center (Szzx201506). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for animal experimental investigations.

Additional information

Funding

This study was supported by the National Key R&D Program of China (2017YFE0103700); the National Natural Science Foundation of China Grants 81172128 (Y Tian), 81372411 (Y Tian); the Jiangsu Provincial Special Program of Clinical Medical Science (BL2014040); Project of Jiangsu Natural Science Foundation (BK20171224); Suzhou Cancer Clinical Medical Center (Szzx201506). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.