Space-like 56Fe irradiation manifests mild, early sex-specific behavioral and neuropathological changes in wildtype and Alzheimer's-like transgenic mice

Sci Rep. 2019 Aug 20;9(1):12118. doi: 10.1038/s41598-019-48615-1.

Abstract

Space travel will expose people to high-energy, heavy particle radiation, and the cognitive deficits induced by this exposure are not well understood. To investigate the short-term effects of space radiation, we irradiated 4-month-old Alzheimer's disease (AD)-like transgenic (Tg) mice and wildtype (WT) littermates with a single, whole-body dose of 10 or 50 cGy 56Fe ions (1 GeV/u) at Brookhaven National Laboratory. At ~1.5 months post irradiation, behavioural testing showed sex-, genotype-, and dose-dependent changes in locomotor activity, contextual fear conditioning, grip strength, and motor learning, mainly in Tg but not WT mice. There was little change in general health, depression, or anxiety. Two months post irradiation, microPET imaging of the stable binding of a translocator protein ligand suggested no radiation-specific change in neuroinflammation, although initial uptake was reduced in female mice independently of cerebral blood flow. Biochemical and immunohistochemical analyses revealed that radiation reduced cerebral amyloid-β levels and microglia activation in female Tg mice, modestly increased microhemorrhages in 50 cGy irradiated male WT mice, and did not affect synaptic marker levels compared to sham controls. Taken together, we show specific short-term changes in neuropathology and behaviour induced by 56Fe irradiation, possibly having implications for long-term space travel.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Behavior, Animal / radiation effects
  • Brain / pathology*
  • Brain / physiopathology
  • Brain / radiation effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Iron Radioisotopes / adverse effects*
  • Learning / radiation effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / pathology
  • Microglia / physiology
  • Microglia / radiation effects
  • Motor Activity / radiation effects
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Sex Factors
  • Space Flight*

Substances

  • Amyloid beta-Peptides
  • Iron Radioisotopes
  • PSEN1 protein, human
  • Presenilin-1