Abstract
BackgroundPrevious studies have shown that beta amyloid (Aβ) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signal-regulated kinase (ERK) cascade. In this study we sought to characterize the cellular localization of phosphorylated, active ERK in organotypic hippocampal cultures after acute exposure to either Aβ (1-42) or nicotine.ResultsWe observed that Aβ and nicotine increased the levels of active ERK in distinct cellular localizations. We also examined whether phospho-ERK was regulated by redox signaling mechanisms and found that increases in active ERK induced by Aβ and nicotine were blocked by inhibitors of NADPH oxidase.ConclusionOur findings indicate that NADPH oxidase-dependent redox signaling is required for Aβ-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease.
Highlights
Previous studies have shown that beta amyloid (Aβ) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signalregulated kinase (ERK) cascade
Treatment with Aβ resulted in the activation of ERK in both neuronal cell bodies and dendrites, as phospho-ERK immunoreactivity was present in stratum pyramidale and stratum radiatum of hippocampal area CA1 (Figure 1A and 1B)
Neither Aβ nor nicotine appeared to cause activation of active ERK in either astrocytes (Figure 1D) or microglia (Figure 1E). These observations suggest that the activation of ERK after either Aβ or nicotine treatment is restricted to neurons and is not present in glial cells
Summary
Previous studies have shown that beta amyloid (Aβ) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signalregulated kinase (ERK) cascade. It has been demonstrated that acute treatment of organotypic hippocampal cultures with nanomolar concentrations of oligomeric Aβ (1-42) leads to the activation of extracellular signal-regulated kinase (ERK) via the alpha 7 nicotinic acetylcholine receptor (α 7nAChR) [3,4]. This signaling cascade involves an increase in calcium and activation of ERK mediated by phosphoinositide-3 kinase (PI3K), which is followed by increases in CREB phosphorylation [3,4,5,6]. The activation of different signaling cascades by Aβ and nicotine (page number not for citation purposes)
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