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.