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Early postnatal irradiation‐induced age‐dependent changes in adult mouse brain: MRI based characterization

Authors
  • Ren, Bo Xu1
  • Huen, Isaac2
  • Wu, Zi Jun3
  • Wang, Hong4
  • Duan, Meng Yun1
  • Guenther, Ilonka5
  • Bhanu Prakash, K. N.2
  • Tang, Feng Ru4
  • 1 Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei, 434023, China , Jingzhou (China)
  • 2 Agency for Science, Technology and Research (A*STAR), Singapore, 138667, Singapore , Singapore (Singapore)
  • 3 Sichuan University, Chengdu, China , Chengdu (China)
  • 4 National University of Singapore, CREATE Tower, 1 CREATE Way #04-01, Singapore, 138602, Singapore , Singapore (Singapore)
  • 5 National University of Singapore, #05-02, 28 Medical Drive, Singapore, 117456, Singapore , Singapore (Singapore)
Type
Published Article
Journal
BMC Neuroscience
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Apr 21, 2021
Volume
22
Issue
1
Identifiers
DOI: 10.1186/s12868-021-00635-2
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundBrain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis.ResultsWe found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10.ConclusionsThe early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.

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