Chronic Low-Dose-Rate Radiation-Induced Persistent DNA Damage and miRNA/mRNA Expression Changes in Mouse Hippocampus...

Area of Science:

• Neuroscience
• Radiation Biology
• Genomics

Background:

• Previous studies linked acute high-dose-rate gamma irradiation to depression and neuropathology.
• Chronic low-dose-rate irradiation effects on the hippocampus and associated molecular changes remain less understood.

Purpose of the Study:

• To investigate the long-term effects of chronic low-dose-rate gamma irradiation on mouse behavior, hippocampal cellular integrity, and molecular profiles.
• To identify specific microRNA (miRNA) and messenger RNA (mRNA) changes in the hippocampus and blood following chronic irradiation.

Main Methods:

• Neurobehavioral tests (open field, light-dark box, elevated plus maze, tail suspension, forced swim) assessed anxiety and depression.
• Immunohistochemistry examined neuronal and glial markers (NeuN, DCX, IBA1, GFAP, PDGFRα) and DNA damage (γH2AX foci).
• miRNA and mRNA sequencing, alongside qRT-PCR, analyzed molecular expression in the hippocampus and blood.

Main Results:

• Chronic low-dose-rate gamma irradiation did not significantly impact body weight or induce behavioral changes related to anxiety or depression.
• No significant loss of mature/immature neurons or inflammatory glial response was observed, but γH2AX foci increased, indicating persistent DNA damage.
• Hippocampal expression of miR-448-3p and miR-361-5p increased, while miR-193a-3p decreased; altered mRNA expression of Fli1, Hs3st5, and Eif4ebp2 was noted.
• Blood analysis revealed increased miR-6967-3p and decreased S1pr5 expression.

Conclusions:

• Chronic low-dose-rate gamma irradiation induces persistent DNA damage foci in the mouse hippocampus without overt behavioral or cellular pathology.
• Specific miRNA and mRNA expression changes in the hippocampus and blood may be molecular indicators of radiation-induced DNA damage.
• These molecular alterations, particularly the interactions between identified miRNAs and mRNAs, warrant further investigation for their role in radiation response.