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Neuroprotective Effects of Apocynin and Galantamine During the Chronic Administration of Scopolamine in an Alzheimer’s Disease Model

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Abstract

Alzheimer’s disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aβ) and oxidative stress in vivo is the scopolamine model. In the present work, the chronic administration (6 weeks) of scopolamine was used to analyze the neuroprotective effects of apocynin and galantamine. The results showed that scopolamine induced cognitive impairment, which was evaluated 24 h after the final dose was administered. In addition, after scopolamine administration, the Aβ and superoxide anion levels were increased, and NADPH oxidase 2 (NOX2), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa B (NFkB) genes were overexpressed. These effects were not observed when either apocynin or galantamine was administered during the last 3 weeks of scopolamine treatment, and although the results from both molecules were related to lower Aβ production and, consequently, lower superoxide anion production, they were likely realized through different pathways. That is, both apocynin and galantamine diminished NADPH oxidase expression, but their effects on transcription factor expression differed. Moreover, experiments in silico showed that galantamine did not interact with the active site of beta secretase, whereas diapocynin, an apocynin metabolite, interacted with the beta-site APP-cleaving enzyme (BACE1) at the catalytic site.

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Funding

This work was supported by grants from Consejo Nacional de Ciencia y Tecnología CB286653, SIPCOFAA-IPN, SIP20195089 for MCRH and CONACYT 254600 and 782 for JCB and scholarships from Consejo Nacional de Ciencia y Tecnología to study MD to EJ.

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Authors and Affiliations

  1. Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, México City, México

    Eliezer Joseph, Daniel Miguel Ángel Villalobos-Acosta, Iohanan Daniel García-Marín & Martha Cecilia Rosales-Hernández

  2. Unidad Periférica de Neurociencias, Facultad de Medicina UNAM, Instituto Nacional de Neurología y Neurocirugía, MVS-SSA, Insurgentes sur 3877, La Fama, Tlalpan, 14269, México City, México

    Mónica Adriana Torres-Ramos

  3. Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Mexico City, Mexico

    Eunice Dalet Farfán-García

  4. Laboratorio de biología molecular, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, México

    Modesto Gómez-López & Ángel Miliar-García

  5. Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, México City, México

    Manuel Jonathan Fragoso-Vázquez

  6. Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México City, México

    José Correa-Basurto

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  1. Eliezer Joseph
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  2. Daniel Miguel Ángel Villalobos-Acosta
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Correspondence to Martha Cecilia Rosales-Hernández.

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Joseph, E., Villalobos-Acosta, D.M.Á., Torres-Ramos, M.A. et al. Neuroprotective Effects of Apocynin and Galantamine During the Chronic Administration of Scopolamine in an Alzheimer’s Disease Model. J Mol Neurosci 70, 180–193 (2020). https://doi.org/10.1007/s12031-019-01426-5

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