Effects of Increased Iron Intake During the Neonatal Period on the Brain of Adult AβPP/PS1 Transgenic Mice

Article type: Research Article

Authors: Fernandez, Liana Lisboa^{a; b; c; *} | Carmona, Marga^c | Portero-Otin, Manuel^d | Naudi, Alba^d | Pamplona, Reinald^d | Schröder, Nadja^a | Ferrer, Isidro^c

Affiliations: [a] Neurobiology and Developmental Biology Laboratory, Pontifical Catholic University, Porto Alegre, RS, Brazil | [b] Health Basic Science Department, Federal University of Medical Science, Porto Alegre, RS, Brazil | [c] Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de LLobregat, CIBERNED, Spain | [d] Department of Experimental Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain

Correspondence: [*] Correspondence to: Liana Lisboa Fernandez, Rua Coronel Bordini, 675, sala 204, Porto Alegre, CEP 90440-001, RS, Brasil. Tel.: +55 51 33325983; E-mail: llfernandez@plugin.com.br.

Note: [] Handling Associate Editor: Sigfrido Scarpa

Abstract: The present study was aimed to investigate neuropathological changes in AβPP/PS1 transgenic mice (Tg), as a model of Alzheimer's disease, subjected to supplementary iron administration in a critical postnatal period, in order to reveal the interaction of genetic and environmental risk factors in the pathogenesis of the disease. Twelve Tg and 10 wild-type (Wt) littermates were administered iron between the 12th and 14th post-natal days (TgFe, WtFe); 11 Tg and 15 Wt received vehicle (sorbitol 5%) alone in the same period (TgSb, WtSb). Mice were killed at the age of six months and processed for morphological and biochemical studies. No modifications in amyloid-β burden were seen in iron-treated and non-iron-treated AβPP/PS1 mice. No differences in microglial reactions were observed when comparing the four groups of mice. Yet increased astrocytosis, as revealed by densitometry of GFAP-immunoreactive astrocytes, and increased expression levels of GFAP, as revealed by gel electrophoresis and western blotting, were found in iron-treated mice (both Tg and Wt) when compared with TgSb and WtSb. This was accompanied by significant changes in brain fatty acid composition in AβPP/PS1 mice that led to a lower membrane peroxidizability index and to reduced protein oxidative damage, as revealed by reduced percentages of the oxidative stress markers: glutamic semialdehyde, aminoadipic semialdehyde, Nε-carboxymethyl-lysine, Nε-carboxyethyl-lysine, and Nε-malondialdehyde-lysine. These findings demonstrate that transient dietary iron supplementation during the neonatal period is associated with cellular and metabolic imprinting in the brain in adult life, but it does not interfere with the appearance of amyloid plaques in AβPP/PS1 transgenic mice.

Keywords: AβPP/PS1 transgenic mice, Alzheimer's disease, docosahexaenoic acid, docosapentaenoic acid, GFAP, iron, neurodegeneration, peroxidizability index, protein oxidation

DOI: 10.3233/JAD-2010-1304

Journal: Journal of Alzheimer's Disease, vol. 19, no. 3, pp. 1069-1080, 2010