Lithium protects hippocampal progenitors, cognitive performance and hypothalamus-pituitary function after irradiation to the juvenile rat brain

Kai Zhou, Cuicui Xie, Malin Wickström, Amalia M Dolga, Yaodong Zhang, Tao Li, Yiran Xu, Carsten Culmsee, Per Kogner, Changlian Zhu, Klas Blomgren

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Abstract

Cranial radiotherapy in children typically causes delayed and progressive cognitive dysfunction and there is no effective preventive strategy for radiation-induced cognitive impairments. Here we show that lithium treatment reduced irradiation-induced progenitor cell death in the subgranular zone of the hippocampus, and subsequently ameliorated irradiation-reduced neurogenesis and astrogenesis in the juvenile rat brain. Irradiation-induced memory impairment, motor hyperactivity and anxiety-like behaviour were normalized by lithium treatment. Late-onset irradiation-induced hypopituitarism was prevented by lithium treatment. Additionally, lithium appeared relatively toxic to multiple cultured tumour cell lines, and did not improve viability of radiated DAOY cells in vitro. In summary, our findings demonstrate that lithium can be safely administered to prevent both short- and long-term injury to the juvenile brain caused by ionizing radiation.

Original languageEnglish
Pages (from-to)34111-34127
Number of pages17
JournalOncotarget
Volume8
DOIs
Publication statusPublished - 16-Mar-2017

Keywords

  • Journal Article
  • YOUNG-MOUSE BRAIN
  • NEURAL STEM/PROGENITOR CELLS
  • CENTRAL-NERVOUS-SYSTEM
  • LONG-TERM
  • CRANIAL IRRADIATION
  • HYPOXIA-ISCHEMIA
  • ACTIVATED MICROGLIA
  • RADIATION-THERAPY
  • CNS MALIGNANCIES
  • NEUROGENESIS

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