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

Eliezer Joseph, Daniel Miguel Ángel Villalobos-Acosta, Mónica Adriana Torres-Ramos, Eunice Dalet Farfán-García, Modesto Gómez-López, Ángel Miliar-García, Manuel Jonathan Fragoso-Vázquez, Iohanan Daniel García-Marín, José Correa-Basurto, Martha Cecilia Rosales-Hernández

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22 Scopus citations

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.

Original languageEnglish
Pages (from-to)180-193
Number of pages14
JournalJournal of Molecular Neuroscience
Volume70
Issue number2
DOIs
StatePublished - 1 Feb 2020

Keywords

  • Alzheimer disease
  • Amyloid beta
  • Apocynin
  • NADPH oxidase
  • Scopolamine

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