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Iron leads to memory impairment that is associated with a decrease in acetylcholinesterase pathways.

Abstract
Increasing evidence indicates that excessive iron in selective regions of the brain may be involved in the etiology of neurodegenerative disorders. Accordingly, increased levels of iron have been described in brain regions of patients in Parkinson's and Alzheimer's diseases. We have characterized neonatal iron loading in rodents as a novel experimental model that mimics the brain iron accumulation observed in patients with neurodegenerative diseases and produces severe cognitive impairment in the adulthood. In the present study we have investigated the involvement of the cholinergic system on iron-induced memory impairment. The effects of a single administration of the acetylcholinesterase (AChE) inhibitor galantamine or the muscarinic receptor agonist oxotremorine on iron-induced memory deficits in rats were examined. Male Wistar rats received vehicle or iron (10.0 mg/kg) orally at postnatal days 12 to 14. At the age of 2-3 months, animals were trained in a novel object recognition task. Iron-treated rats showed long-term impairments in recognition memory. The impairing effect was reversed by systemic administration of galantamine (1 mg/kg) immediately after training. In addition, iron-treated rats that received oxotremorine (0.5 mg/kg) showed enhanced memory retention. Rats given iron showed a decreased AChE activity in the striatum when compared to controls. The results suggest that, at least in part, iron-induced cognitive deficits are related to a dysfunction of cholinergic neural transmission in the brain. These findings might have implications for the development of novel therapeutic strategies aimed at ameliorating cognitive decline associated with neurodegenerative disorders.
AuthorsVinícius Pieta Perez, Maria Noêmia Martins de Lima, Rosane Souza da Silva, Arethuza Silva Dornelles, Gustavo Vedana, Maurício Reis Bogo, Carla Denise Bonan, Nadja Schröder
JournalCurrent neurovascular research (Curr Neurovasc Res) Vol. 7 Issue 1 Pg. 15-22 (Feb 2010) ISSN: 1875-5739 [Electronic] United Arab Emirates
PMID20158466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cholinesterase Inhibitors
  • Ferrous Compounds
  • Muscarinic Agonists
  • Galantamine
  • Oxotremorine
  • ferrous succinate
  • Acetylcholinesterase
Topics
  • Acetylcholinesterase (metabolism)
  • Administration, Oral
  • Animals
  • Animals, Newborn
  • Brain (enzymology, growth & development)
  • Cholinesterase Inhibitors (therapeutic use)
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Exploratory Behavior (drug effects)
  • Female
  • Ferrous Compounds (administration & dosage)
  • Galantamine (therapeutic use)
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Male
  • Memory Disorders (chemically induced, enzymology, pathology)
  • Muscarinic Agonists (therapeutic use)
  • Neural Pathways (enzymology, pathology)
  • Oxotremorine (therapeutic use)
  • Pregnancy
  • Rats
  • Reaction Time (drug effects)
  • Recognition, Psychology (drug effects)
  • Statistics, Nonparametric

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