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

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.

Implications of prion protein biology.

The cellular prion protein (PrPc) is a protein found on the cell surface of many cell subtypes, especially neurons, anchored by a glycosyl-phosphatidylinositol residue. The physiological role of PrPc is still not understood. However, it is known that participates in copper uptake, protection against oxidative stress, cell adhesion, differentiation, signalling and cell survival. Moreover, it is also involved in memory formation. Despite the numerous functions given to PrPc, its discovery did not occur due to its altered isoform involvement (PrPsc) as an infectious agent of spongiform encephalopathies These diseases are unique because they can be hereditary, sporadic or have an acquired etiology. Much has been done concerning this intriguing protein, but there is still the need for more studies to truly understand PrPc functions and PrPsc pathogenesis mechanisms. In this way, new and more effective therapeutical approaches can be developed, and more information on other amyloid diseases can be gathered.