title: Differential susceptibility following beta-amyloid peptide-(1-40) administration in C57BL/6 and Swiss albino mice: Evidence for a dissociation between cognitive deficits and the glutathione system response.
abstract: Considerable evidence supports the role of oxidative stress in the pathogenesis of Alzheimer's disease (AD). Previous studies suggest that the central nervous system (CNS) administration of beta-amyloid peptide, the major constituent of senile plaque in AD, induces oxidative stress in rodents which may contribute to the learning and memory deficits verified in the beta-amyloid model of AD. In the present study, we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated beta-amyloid peptide-(1-40) (Abeta(1-40)) (400pmol/mouse) on spatial learning and memory performance, synaptic density and the glutathione (GSH)-dependent antioxidant status in adult male C57BL/6 and Swiss albino mice. Seven days after Abeta(1-40) administration, C57BL/6 and Swiss mice presented similar spatial learning and memory impairments, as evaluated in the water maze task, although these impairments were not found in Abeta(40-1)-treated mice. Moreover, a similar decline of synaptophysin levels was observed in the hippocampus (HC) and prefrontal cortex (PFC) of both Swiss and C57BL/6 mice treated with Abeta(1-40), which suggests synaptic loss. C57BL/6 mice presented lower levels of glutathione-related antioxidant defences (total glutathione (GSH-t) levels, glutathione peroxidase (GPx) and glutathione reductase (GR) activity) in the HC and PFC in comparison to Swiss mice. Despite the reduced basal GSH-dependent antioxidant defences observed in C57BL/6 mice, Abeta(1-40) administration induced significant alterations in the brain antioxidant parameters only in Swiss mice, decreasing GSH-t levels and increasing GPx and GR activity in the HC and PFC 24h after treatment. These results indicate strain differences in the susceptibility to Abeta(1-40)-induced changes in the GSH-dependent antioxidant defences in mice, which should be taken into account in further studies using the Abeta model of AD in mice. In addition, the present findings suggest that the spatial learning and memory deficits induced by beta-amyloid peptides in rodents may not be entirely related to glutathione-dependent antioxidant response.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Rui D S
authors.initials: RD
authors.lastname: Prediger
authors.forename: Jeferson L
authors.initials: JL
authors.lastname: Franco
authors.forename: Pablo
authors.initials: P
authors.lastname: Pandolfo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Medeiros
authors.forename: Filipe S
authors.initials: FS
authors.lastname: Duarte
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Giunta
authors.forename: Cláudia P
authors.initials: CP
authors.lastname: Figueiredo
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Takahashi
authors.forename: Alcir L
authors.initials: AL
authors.lastname: Dafre
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D004198:Disease Susceptibility; D005106:Exploratory Behavior / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage*; D011930:Reaction Time / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013045:Species Specificity
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C090308:amyloid beta-protein (40-1); D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione