Sub-chronic oral cinnamaldehyde treatment prevents scopolamine-induced memory retrieval deficit and hippocampal Akt and MAPK dysregulation in male mice.

Objectives: Cholinergic system dysfunction was found to play a key role in Alzheimer's disease (AD) pathogenesis. Therefore, the animal model of scopolamine-induced amnesia has been widely used in AD researches. Cinnamon, as a spice commonly used in cuisine, has been shown to exert some therapeutic effects. The most abundant compound in cinnamon is cinnamaldehyde which recently was shown to exert several neuroprotective effects in animal models. Therefore, this study aimed to assess whether cinnamaldehyde has the potency to prevent memory retrieval impairment and hippocampal protein kinase B (Akt) and MAPK (extracellular signal-regulated kinase (ERK)) alterations induced by scopolamine in mice.Methods: Adult male mice were pretreated with cinnamaldehyde (12.5, 25, 40 and 100 mg/kg/oral gavage) 10 days before training. The training of passive avoidance task was performed on the 10^th day and a memory retention test was done 24 h later. Scopolamine (1 mg/kg) was injected intraperitoneally, 30 min before the retention test to induce memory retrieval deficit. At the complement of the behavioral experiments, the hippocampi were isolated for western blot analysis to assess the phosphorylated and total levels of hippocampal MAPK and Akt proteins.Results: The results showed that cinnamaldehyde pretreatment at the dose of 100 mg/kg significantly prevented the amnesic effect of scopolamine. Furthermore, cinnamaldehyde prevented scopolamine induced dysregulations of hippocampal MAPK and Akt.Discussion: The results of the present study revealed that oral sub-chronic cinnamaldehyde administration has the capability to prevent memory retrieval deficit induced by cholinergic blockade and restores hippocampal MAPK and Akt dysregulations.