title: Induction of apoptotic change in the rat hippocampus caused by ferric nitrilotriacetate.
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.
authors.affiliation: Okayama University Hospital, Japan. maedas@md.okayama-u.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Maeda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Arai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Higuchi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tomoyasu
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Mizuno
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000818:Animals; D017209:Apoptosis; D005290:Ferric Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D011976:Receptors, Muscarinic / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods
chemical_list: D005290:Ferric Compounds; D011976:Receptors, Muscarinic; D006861:Hydrogen Peroxide; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate