Early biochemical and morphological modifications in the brain of a transgenic mouse model of Alzheimer's disease: a role for peroxisomes.
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.
Cimini
AnnaMaria
A
Department of Basic and Applied Biology, University of L'Aquila, 67010 L'Aquila, Italy.
Moreno
Sandra
S
D'Amelio
Marcello
M
Cristiano
Loredana
L
D'Angelo
Barbara
B
Falone
Stefano
S
Benedetti
Elisabetta
E
Carrara
Paolo
P
Fanelli
Francesca
F
Cecconi
Francesco
F
Amicarelli
Fernanda
F
Cerù
Maria Paola
MP
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D002374:Catalase