Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice

Int J Radiat Biol. 2016 Jul;92(7):371-9. doi: 10.3109/09553002.2016.1164911. Epub 2016 Apr 4.

Abstract

Purpose: To investigate whether neonatal exposure to fractionated external gamma radiation and co-exposure to radiation and nicotine can affect/exacerbate developmental neurotoxic effects, including altered behavior/cognitive function and the susceptibility of the cholinergic system in adult male mice.

Materials and methods: Neonatal male Naval Medical Research Institute (NMRI) mice were irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 μg/kg b.w.) twice daily on postnatal day (PND) 10, 10-11, 10-12 or 10-13 (nicotine only). At 2 months of age the animals were tested for spontaneous behavior in a novel home environment, habituation capacity and nicotine-induced behavior.

Results: Fractionated irradiation and co-exposure to radiation and nicotine on three consecutive days disrupted behavior and habituation and altered susceptibility of the cholinergic system. All observed effects were significantly more pronounced in mice co-exposed to both radiation and nicotine.

Conclusions: The fractionated irradiation regime affects behavior/cognitive function in a similar manner as has previously been observed for single-dose exposures. Neonatal co-exposure to radiation and nicotine, during a critical period of brain development in general and cholinergic system development in particular, enhance these behavioral defects suggesting that the cholinergic system can be a target system for this type of developmental neurotoxic effects.

Keywords: Low-dose radiation; behavior; brain development; cholinergic system; cognition; nicotine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavioral Symptoms / etiology*
  • Behavioral Symptoms / physiopathology
  • Brain / drug effects
  • Brain / radiation effects*
  • Cholinergic Neurons / drug effects*
  • Cholinergic Neurons / radiation effects
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / physiopathology
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Gamma Rays / adverse effects
  • Male
  • Mice
  • Nicotine / toxicity*
  • Radiation Tolerance / drug effects*

Substances

  • Nicotine