Memantine prevents reference and working memory impairment caused by sleep deprivation in both young and aged Octodon degus

Ernesto Tarragon, Dolores Lopez, Cristina Estrada, Ana Gonzalez-Cuello, Carmen Ma Ros, Yves Lamberty, Fabien Pifferi, Massimo Cella, Mara Canovi, Giovanna Guiso, Marco Gobbi, Emiliano Fernández-Villalba, Olivier Blin, Regis Bordet, Jill C. Richardson, María Trinidad Herrero

Research output: Contribution to journalArticlepeer-review

Abstract

Memory loss is one of the key features of cognitive impairment in either aging, Mild Cognitive Impairment (MCI) or dementia. Pharmacological treatments for memory loss are today focused on addressing symptomatology. One of these approved compounds is memantine, a partial NMDA receptor antagonist that has proved its beneficial effects in cognition. The Octodon degus (O. degus) has been recently proposed as a potential model relevant for neurodegenerative diseases. However, there are no previous studies investigating the effect of pharmacological treatments for age-related cognitive impairment in this rodent. In this work we aimed to evaluate the effect of memantine on sleep deprivation (SD)-induced memory impairment in young and old O. degus. Young and old animals were trained in different behavioral paradigms validated for memory evaluation, and randomly assigned to a control (CTL, n = 14) or an SD (n = 14) condition, and treated with vehicle or memantine (10-mg/Kg i.p.) before the SD started. We demonstrate that SD impairs memory in both young and old animals, although the effect in the old group was significantly more severe (P <0.05). Memantine pretreatment was able to prevent the cognitive impairment caused by SD in both age groups, while it had no negative effect on CTL animals. The positive effect of memantine in counteracting the negative effect of SD on the retrieval process even in the aged O. degus further supports the translational potential of both the challenge and the species, and will enable a better understanding of the behavioral features of memantine effects, especially related with reference and working memories.

Original languageEnglish
Pages (from-to)206-214
Number of pages9
JournalNeuropharmacology
Volume85
DOIs
Publication statusPublished - 2014

Keywords

  • Alzheimer disease
  • Memantine
  • Memory
  • Octodon degus
  • Sleep deprivation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology
  • Medicine(all)

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