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Intracerebroventricular Streptozotocin as a Model of Alzheimer’s Disease: Neurochemical and Behavioral Characterization in Mice

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Abstract

Streptozotocin has been widely used to mimic some aspects of Alzheimer’s disease (AD). However, especially in mice, several characteristics involved in the streptozotocin (STZ)-induced AD pathology are not well known. The main purpose of this study was to evaluate temporally the expression of AD-related proteins, such as amyloid-β (Aβ), choline acetyltransferase (ChAT), synapsin, axonal neurofilaments, and phosphorylated Tau in the hippocampus following intracerebroventricular (icv) administration of STZ in adult mice. We also analyzed the impact of STZ on short- and long-term memory by novel object recognition test. Male mice were injected with STZ or citrate buffer, and AD-related proteins were evaluated by immunoblotting assays in the hippocampus at 7, 14, or 21 days after injection. No differences between the groups were found at 7 days. The majority of AD markers evaluated were found altered at 14 days, i.e., the STZ group showed increased amyloid-β protein and neurofilament expression, increased phosphorylation of Tau protein, and decreased synapsin expression levels compared to controls. Except for synapsin, all of these neurochemical changes were transient and did not last up to 21 days of STZ injection. Moreover, both short-term and long-term memory deficits were demonstrated after STZ treatment at 14 and 21 days after STZ treatment.

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Acknowledgements

Work supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), University of Sao Paulo—Núcleo de Apoio à Pesquisa em Neurociência Aplicada (NAPNA) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). K.G. R, B.R.A., and M.S.H. were the recipients of fellowships from FAPESP. Thanks are due to Adilson S. Alves for the technical assistance.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Professor Lineu Prestes, CEP 05508-900, Sao Paulo, 1524, Brazil

    Katherine Garcia Ravelli, Barbara dos Anjos Rosário, Marina Sorrentino Hernandes & Luiz Roberto Britto

  2. Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil

    Rosana Camarini

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  1. Katherine Garcia Ravelli
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  2. Barbara dos Anjos Rosário
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  3. Rosana Camarini
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  4. Marina Sorrentino Hernandes
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Correspondence to Marina Sorrentino Hernandes.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Ravelli, K.G., Rosário, B.d.A., Camarini, R. et al. Intracerebroventricular Streptozotocin as a Model of Alzheimer’s Disease: Neurochemical and Behavioral Characterization in Mice. Neurotox Res 31, 327–333 (2017). https://doi.org/10.1007/s12640-016-9684-7

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  • DOI: https://doi.org/10.1007/s12640-016-9684-7

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