Differential expression of egr1 and activation of microglia following irradiation in the rat brain

Strahlenther Onkol. 2007 May;183(5):248-55. doi: 10.1007/s00066-007-1664-7.

Abstract

Background: Little is known about the immediate effects of whole-brain gamma-irradiation. The authors hypothesize that Egr1 as an immediate early gene and microglia both participate in early reactions.

Material and methods: Both, expression of Egr1 and cellular distribution were studied in a temporal sequence in different brain regions of rats subjected to irradiation with 10 Gy. Brain tissue was examined using immunohistochemistry, real-time RT-PCR (reverse transcription-polymerase chain reaction), and Western blotting.

Results: Astroglia and oligodendroglia showed increased Egr1 immunoreactivity within the first hours following irradiation. This was accompanied by a strong peak in CD68 immunoreactivity histologically attributable to activated microglia. A high constitutive expression of Egr1 protein in the nuclei of activated neurons was reduced following irradiation and RT-PCR demonstrated significantly reduced levels of egr1-lv as a neuronal activity-related mRNA variant.

Conclusion: The induction of Egr1 in glial cells, as well as the activation of microglia take place earlier than histological changes reported so far. The authors revealed a temporal sequence of reactions that point toward the initiation of an immediate inflammatory response including reduced neuronal activity.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Astrocytes / pathology
  • Astrocytes / radiation effects
  • Brain / pathology
  • Brain / radiation effects*
  • Cell Nucleus / pathology
  • Cell Nucleus / radiation effects
  • Cerebellum / pathology
  • Cerebellum / radiation effects
  • Cranial Irradiation / adverse effects*
  • Cytoplasm / pathology
  • Cytoplasm / radiation effects
  • Dentate Gyrus / pathology
  • Dentate Gyrus / radiation effects
  • Early Growth Response Protein 1 / genetics*
  • Frontal Lobe / pathology
  • Frontal Lobe / radiation effects
  • Gene Expression / radiation effects
  • Hippocampus / pathology
  • Hippocampus / radiation effects
  • Male
  • Microglia / radiation effects*
  • Neurons / pathology
  • Neurons / radiation effects
  • Parietal Lobe / pathology
  • Parietal Lobe / radiation effects
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics*
  • Radiation Injuries, Experimental / genetics*
  • Radiation Injuries, Experimental / pathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • RNA, Messenger