Animals
Cerebral Cortex/*metabolism
Cotinine/*pharmacology
Cyclic AMP Response Element-Binding Protein/metabolism
Male
Memory/*drug effects
Mice
Mice, Transgenic
Phosphorylation/drug effects
Recognition (Psychology)/*drug effects
Visual Perception/*drug effects
tau Proteins/*metabolism
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 beta peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3beta (GSK3beta) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3beta 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.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 beta peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3beta (GSK3beta) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3beta 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.