Cotinine improves visual recognition memory and decreases cortical Tau phosphorylation in the Tg6799 mice

J. Alex Grizzell, Sagar Patel, George E. Barreto, Valentina Echeverria

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is associated with the progressive aggregation of hyperphosphorylated forms of the microtubule associated protein Tau in the central nervous system. Cotinine, the main metabolite of nicotine, reduced working memory deficits, synaptic loss, and amyloid β peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3β (GSK3β) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3β sites Serine (Ser)-396/Ser-404 and phospho-CREB were investigated in the Tg6799 and non-transgenic (NT) littermate mice. Tg mice showed short-term visual recognition memory impairment in the novel object recognition test, and higher levels of Tau phosphorylation when compared to NT mice. Cotinine significantly improved visual recognition memory performance increased CREB phosphorylation and reduced cortical Tau phosphorylation. Potential mechanisms underlying theses beneficial effects are discussed.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume78
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cotinine
  • CREB
  • Memory
  • Tau

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