Induction of apoptotic change in the rat hippocampus caused by ferric nitrilotriacetate

Redox Rep. 2011;16(3):114-20. doi: 10.1179/174329211X13049558293597.

Abstract

Iron, a source of oxidative stress, plays a major role in the pathology of neurodegenerative disease. In Alzheimer's disease, the hippocampus is vulnerable to oxidative stress, leading to impairment in memory formation. In our previous study, a brain oxidative reaction was induced after intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA). However, since only a small amount of iron reached the brain in the previous study, Fe-NTA was administered into the hippocampus using an osmotic pump in this study. After continuous injection of Fe-NTA for 2 weeks, a high level of apoptotic change was induced in the hippocampus, in accordance with the iron localization. After injection for 4 weeks, the hippocampus was totally destroyed. A small amount of iron infiltrated into the cerebral cortex and the striatum, and deposition was observed at the choroid plexus and ependymal cells. However, no apoptotic reaction or clear tissue injury was observed in these areas. In addition, muscarinic acetylcholine receptors (M1, M2, and M4) were decreased in both the cortex and hippocampus while it increased in the striatum. Thus, the hippocampus is likely vulnerable to oxidative stress from Fe-NTA, and the oxidative stress is considered to bring the disturbance in the muscarinic acetylcholine receptors.

MeSH terms

  • Animals
  • Apoptosis*
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Hydrogen Peroxide / administration & dosage
  • Hydrogen Peroxide / pharmacology
  • Male
  • Mice
  • Nitrilotriacetic Acid / administration & dosage
  • Nitrilotriacetic Acid / analogs & derivatives*
  • Nitrilotriacetic Acid / pharmacology
  • Oxidation-Reduction
  • Oxidative Stress*
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Receptors, Muscarinic / metabolism
  • Staining and Labeling / methods

Substances

  • Ferric Compounds
  • Receptors, Muscarinic
  • Hydrogen Peroxide
  • Nitrilotriacetic Acid
  • ferric nitrilotriacetate