Loss of hippocampal neurogenesis, increased novelty-induced activity, decreased home cage activity, and impaired reversal learning one year after irradiation of the young mouse brain

Exp Neurol. 2013 Sep;247:402-9. doi: 10.1016/j.expneurol.2013.01.006. Epub 2013 Jan 16.

Abstract

Radiotherapy is a major cause of long-term complications in survivors of pediatric brain tumors. These complications include intellectual and memory impairments as well as perturbed growth and puberty. We investigated the long-term effects of a single 8 Gy irradiation dose to the brains of 14-day-old mice. Behavior was assessed one year after irradiation using IntelliCage and open field, followed by immunohistochemical investigation of proliferation and neurogenesis in the dentate gyrus of the hippocampus. We found a 61% reduction in proliferation and survival (BrdU incorporation 4 weeks prior to sacrifice), 99% decrease in neurogenesis (number of doublecortin-positive cells) and gliosis (12% higher astrocyte density) one year following irradiation. Irradiated animals displayed increased activity in a novel environment but decreased activity in their home cage. Place learning in the IntelliCage was unaffected by irradiation but reversal learning was impaired. Irradiated animals persevered in visiting previously correct corners to a higher extent compared to control animals. Hence, despite the virtual absence of neurogenesis in these old mice, spatial learning could take place. Reversal learning however, where a previous memory was replaced with a new one, was partly impaired. This model is useful to study the so called late effects of radiotherapy to the young brain and to evaluate possible interventions.

Keywords: Gliosis; IntelliCage; Irradiation; Learning; Memory; Neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • Cell Count
  • Cell Proliferation / radiation effects
  • Disease Models, Animal
  • Exploratory Behavior / radiation effects*
  • Gliosis / etiology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / physiology
  • Motor Activity / radiation effects*
  • Neurogenesis / physiology
  • Neurogenesis / radiation effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Principal Component Analysis
  • Radiation Injuries / complications*
  • Radiation Injuries / pathology*
  • Reversal Learning / physiology*

Substances

  • Bromodeoxyuridine