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A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures

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Abstract

Accumulation of the neurotoxic amyloid β-peptide (Aβ) in the brain is a hallmark of Alzheimer’s disease (AD). Several synthetic Aβ peptides have been used to study the mechanisms of toxicity. Here, we sought to establish comparability between two commonly used Aβ peptides Aβ1-42 and Aβ25-35 on an in vitro model of Aβ toxicity. For this purpose we used organotypic slice cultures of rat hippocampus and observed that both Aβ peptides caused similar toxic effects regarding to propidium iodide uptake and caspase-3 activation. In addition, we also did not observe any effect of both peptides on Akt and PTEN phosphorylation; otherwise the phosphorylation of GSK-3β was increased. Although further studies are necessary for understanding mechanisms underlying Aβ peptide toxicity, our results provide strong evidence that Aβ1-42 and the Aβ25-35 peptides induce neural injury in a similar pattern and that Aβ25-35 is a convenient tool for the investigation of neurotoxic mechanisms involved in AD.

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Acknowledgements

This work was supported the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Pró-Reitoria de Pesquisa da Universidade Federal do Rio Grande do Sul (PROPESQ/UFRGS). The authors thank to Alessandra Heizelmann for excellent technical assistance.

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  1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Av. Ramiro Barcelos, 2600 - anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Rudimar Luiz Frozza, Ana Paula Horn, Juliana Bender Hoppe, Fabrício Simão, Daniéli Gerhardt, Ricardo Argenta Comiran & Christianne Gazzana Salbego

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  1. Rudimar Luiz Frozza
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  2. Ana Paula Horn
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Correspondence to Christianne Gazzana Salbego.

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Frozza, R.L., Horn, A.P., Hoppe, J.B. et al. A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures. Neurochem Res 34, 295–303 (2009). https://doi.org/10.1007/s11064-008-9776-8

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