Deficits in Sustained Attention and Changes in Dopaminergic Protein Levels following Exposure to Proton Radiation Are Related to Basal Dopaminergic Function

PLoS One. 2015 Dec 10;10(12):e0144556. doi: 10.1371/journal.pone.0144556. eCollection 2015.

Abstract

The current report assessed the effects of low-level proton irradiation in inbred adult male Fischer 344 and Lewis rats performing an analog of the human Psychomotor Vigilance Test (PVT), commonly utilized as an object risk assessment tool to quantify fatigue and sustained attention in laboratory, clinical, and operational settings. These strains were used to determine if genetic differences in dopaminergic function would impact radiation-induced deficits in sustained attention. Exposure to head-only proton irradiation (25 or 100 cGy) disrupted rPVT performance in a strain-specific manner, with 25 cGy-exposed Fischer 344 rats displaying the most severe deficits in sustained attention (i.e., decreased accuracy and increased premature responding); Lewis rats did not display behavioral deficits following radiation. Fischer 344 rats displayed greater tyrosine hydroxylase and dopamine transporter levels in the frontal cortex compared to the Lewis rats, even though radiation exposure increased both of these proteins in the Lewis rats only. Tyrosine hydroxylase was decreased in the parietal cortex of both rat strains following radiation exposure, regardless of proton dose. Strain-specific cytokine changes were also found in the frontal cortex, with the Lewis rats displaying increased levels of putative neurotrophic cytokines (e.g., CNTF). These data support the hypothesis that basal dopaminergic function impacts the severity of radiation-induced deficits in sustained attention.

Publication types

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

MeSH terms

  • Animals
  • Attention / physiology
  • Attention / radiation effects*
  • Blotting, Western
  • Brain / metabolism
  • Brain / radiation effects*
  • Ciliary Neurotrophic Factor / metabolism
  • Cytokines / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Frontal Lobe / metabolism
  • Frontal Lobe / radiation effects
  • Humans
  • Male
  • Parietal Lobe / metabolism
  • Parietal Lobe / radiation effects
  • Protons*
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Species Specificity
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Ciliary Neurotrophic Factor
  • Cytokines
  • Dopamine Plasma Membrane Transport Proteins
  • Protons
  • Tyrosine 3-Monooxygenase
  • Dopamine

Grant support

Supported by the National Space Biomedical Research Institute (NSBRI) through NASA cooperative agreement NCC 9-58, grants NBPF01604 (RDH), NBPF02802 (RDH), NBPF04201 (RDH), PF02602 (CMD), EO00010 (CMD), and NASA NNX15AC71G (CMD).