Early Biochemical and Morphological Modifications in the Brain of a Transgenic Mouse Model of Alzheimer's Disease: A Role for Peroxisomes

Article type: Research Article

Authors: Cimini, AnnaMaria^a; | Moreno, Sandra^b; | D'Amelio, Marcello^c | Cristiano, Loredana^a | D'Angelo, Barbara^a | Falone, Stefano^a | Benedetti, Elisabetta^a | Carrara, Paolo^b | Fanelli, Francesca^b | Cecconi, Francesco^{c; d} | Amicarelli, Fernanda^a | Cerù, Maria Paola^{a; *}

Affiliations: [a] Department of Basic and Applied Biology, University of L'Aquila, L'Aquila, Italy | [b] Department of Biology-LIME, University “Roma Tre”, Rome, Italy | [c] IRCCS Fondazione Santa Lucia, Rome, Italy | [d] Dulbecco Telethon Institute, Department of Biology, University of Rome Tor Vergata, Italy

Correspondence: [*] Corresponding author: Maria Paola Cerù, Department of Basic and Applied Biology, University of L'Aquila, Via Vetoio, Loc. Coppito, 67010 L'Aquila, Italy. Tel.: +39 0862 433288; Fax: +39 0862 433273; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: The central role of peroxisomes in reactive oxygen species and lipid metabolism and their importance in brain functioning are well established. The aim of this work has been to study the peroxisomal population in the Tg2576 mouse model of Alzheimer's disease (AD), at the age of three months when no apparent signs of behavioral, neuroanatomical, cytological, or biochemical alterations have been so far described. The expression and localization of peroxisomal (PMP70, CAT, AOX, and THL) and peroxisome-related proteins (PEX5p, GPX1, SOD1, and SOD2) were studied in the neocortex and hippocampus of transgenic and wild-type animals. Oxidative stress markers (TBARS, acrolein, and 8-OHG) were also evaluated. Our results demonstrate that significant alterations are already detectable at this early stage of the disease and also involve peroxisomes. Their number and protein composition change concomitantly with early oxidative stress. Interestingly, the neocortex shows a compensatory response, consisting in an increase of reactive oxygen species scavenging enzymes, while the hippocampus appears more prone to the oxidative insult. This different behavior could be related to metabolic differences in the two brain areas, also involving peroxisome abundance and/or enzymatic content.

Keywords: Acyl-CoA β-oxidation, Alzheimer's disease, antioxidant enzymes, catalase, hippocampus, neocortex, oxidative stress, reactive oxygen species, peroxisomes, Tg2576

DOI: 10.3233/JAD-2009-1199

Journal: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 935-952, 2009