Research Paper Volume 13, Issue 12 pp 15815—15832
Spatiotemporal dynamics of γH2AX in the mouse brain after acute irradiation at different postnatal days with special reference to the dentate gyrus of the hippocampus
- 1 Radiation Physiology Lab, Singapore Nuclear Research and Safety Initiative, National University of Singapore, Singapore 138602, Singapore
- 2 The School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei, China
- 3 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
Received: February 17, 2021 Accepted: June 4, 2021 Published: June 23, 2021https://doi.org/10.18632/aging.203202
How to Cite
Copyright: © 2021 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Gamma H2A histone family member X (γH2AX) is a molecular marker of aging and disease. However, radiosensitivity of the different brain cells, including neurons, glial cells, cells in cerebrovascular system, epithelial cells in pia mater, ependymal cells lining the ventricles of the brain in immature animals at different postnatal days remains unknown. Whether radiation-induced γH2AX foci in immature brain persist in adult animals still needs to be investigated. Hence, using a mouse model, we showed an extensive postnatal age-dependent induction of γH2AX foci in different brain regions at 1 day after whole body gamma irradiation with 5Gy at postnatal day 3 (P3), P10 and P21. P3 mouse brain epithelial cells in pia mater, glial cells in white matter and cells in cerebrovascular system were more radiosensitive at one day after radiation exposure than those from P10 and P21 mice. Persistent DNA damage foci (PDDF) were consistently demonstrated in the brain at 120 days and 15 months after irradiation at P3, P10 and P21, and these mice had shortened lifespan compared to the age-matched control. Our results suggest that early life irradiation-induced PDDF at later stages of animal life may be related to the brain aging and shortened life expectancy of irradiated animals.
ABC: Avidin–biotin complex; AD: Alzheimer's disease; ALS: Amyotrophic lateral sclerosis; ANOVA: Analysis of variance; α-syn: α-synuclein; 53BP1: p53 binding protein 1; BRCA1: Breast cancer susceptibility gene 1; CC: Corpus callosum; CCL: C-C Motif Chemokine Ligand; Chk2: Checkpoint kinase 2; CSPall: Central subpallium/classic basal ganglia; DAB: 3,3′-Diaminobenzidine; DPall: Dorsal pallium; DSB: Double-strand break; γH2AX: Gamma H2A histone family member X; GSK3β: Glycogen synthase kinase 3β; IACUC: Institutional Animal Care and Use Committee; LDL: Low-density lipoprotein; MCI: Mild cognitive impairment; MPall: Medial pallium; P3: postnatal day 3; P10: postnatal day 10; P21: postnatal day 21; PB: Phosphate buffer; PBS: Phosphate buffer saline; PBS-TX: Phosphate buffer saline with 0.1% Triton X-100; PD: Parkinson's disease; PDDF: Persistent DNA damage foci; PGC1α: Peroxisome proliferator–activated receptor gamma coactivator 1 alpha; RMS: Rostral migratory streams; ROS: reactive oxygen species; SGZ: Subgranular zone; SIRT2: Sirtuin 2; SVZ: Subventricular zone; TelA: Alar plate of evaginated telencephalic vesicle; TMS: Temporal migratory streams.