Early intervention in the 3xTg-AD mice with an amyloid beta-antibody fragment ameliorates first hallmarks of alzheimer disease
Por:
Gimenez-Llort, L, Rivera-Hernandez, G, Marin-Argany, M, Sanchez-Quesada, JL, Villegas, S
Publicada:
1 sep 2013
Resumen:
The single-chain variable fragment, scFv-h3D6, has been shown to prevent in vitro toxicity induced by the amyloid (A) peptide in neuroblastoma cell cultures by withdrawing A oligomers from the amyloid pathway. Present study examined the in vivo effects of scFv-h3D6 in the triple-transgenic 3xTg-AD mouse model of Alzheimer disease. Prior to the treatment, five-month-old female animals, corresponding to early stages of the disease, showed the first behavioral and psychological symptoms of dementia -like behaviors. Cognitive deficits included long- and short-term learning and memory deficits and high swimming navigation speed. After a single intraperitoneal dose of scFv-h3D6, the swimming speed was reversed to normal levels and the learning and memory deficits were ameliorated. Brain tissues of these animals revealed a global decrease of A oligomers in the cortex and olfactory bulb after treatment, but this was not seen in the hippocampus and cerebellum. In the untreated 3xTg-AD animals, we observed an increase of both apoJ and apoE concentrations in the cortex, as well as an increase of apoE in the hippocampus. Treatment significantly recovered the non-pathological levels of these apolipoproteins. Our results suggest that the benefit of scFv-h3D6 occurs at both behavioral and molecular levels.
Filiaciones:
Gimenez-Llort, L:
Univ Autonoma Barcelona, Inst Neurociencies, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Psiquiatria & Med Legal, E-08193 Barcelona, Spain
Rivera-Hernandez, G:
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Protein Folding & Stabil Grp, Unitat Biociencies, E-08193 Barcelona, Spain
Marin-Argany, M:
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Protein Folding & Stabil Grp, Unitat Biociencies, E-08193 Barcelona, Spain
Sanchez-Quesada, JL:
Inst Invest Biomed St Pau, Serv Bioquim, Barcelona, Spain
Villegas, S:
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Protein Folding & Stabil Grp, Unitat Biociencies, E-08193 Barcelona, Spain
Bronze, Green Published
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