Effects of sub-chronic caffeine ingestion on memory and the hippocampal Akt, GSK-3ß and ERK signaling in mice.

Caffeine, one of the most widely consumed psychoactive substance in the world, has been shown to affect mood, memory, alertness, and cognitive performance. This study aimed to assess the effect of sub-chronic oral gavage of caffeine on memory and the phosphorylation levels of hippocampal Akt (protein kinase B), GSK-3ß (Glycogen Synthase Kinase-3beta) and ERK (extracellular signal-regulated kinase) in mice. Adult male NMRI mice were administered with caffeine at the doses of 0.25, 0.5, 0.75 and 1.5 mg/kg/oral gavage for 10 days before behavioral assessments. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of Akt, GSK-3ß and ERK proteins. The results showed that sub-chronic caffeine ingestion at the dose of 0.5 mg/kg improves memory in mice both in passive avoidance and novel object recognition tasks. Furthermore, this memory enhancing dose of caffeine elevated the ratios of phosphorylated to total contents of hippocampal Akt, GSK-3ß and ERK. This study suggests that sub-chronic low dose of caffeine improves memory and increases the phosphorylation of hippocampal Akt, GSK-3ß and ERK proteins.

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 10th 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.

The effect of cinnamaldehyde on passive avoidance memory and hippocampal Akt, ERK and GSK-3ß in mice.

Cinnamon, a spice widely used in cuisine, has been reported to exert therapeutic effects. Recently, cinnamon was shown to improve memory in some animal models of memory impairment and in poor learning mice. This study aimed to investigate the effect of cinnamaldehyde, the major compound in cinnamon on passive avoidance memory and activation of hippocampal Akt (protein kinase B), ERK (extracellular signal-regulated kinase) and GSK-3ß (Glycogen Synthase Kinase-3beta) in mice. In the present study, oral cinnamaldehyde at doses of 12.5, 25, 30, 40, 45, 50 and 100 mg/kg/daily was administered to adult male NMRI mice, initiated 10 days before training and continued during training and retention days. Training of passive avoidance task was performed on day 10 and a retention trial was done 24 h after. Upon completion of the retention test, hippocampi were removed for Western blot analysis to detect the phosphorylated and total levels of Akt, ERK and GSK-3ß proteins. Results showed that cinnamaldehyde exerts a biphasic effect on passive avoidance memory by impairing memory at lower doses while improving at higher doses. Moreover, at memory improving doses, cinnamaldehyde increased the phosphorylated forms of hippocampal Akt, ERK and GSK-3ß while these proteins did not change at impairing doses of cinnamaldehyde. For the first time, this study revealed a biphasic effect of cinnamaldehyde on memory as well as indicating that the memory improving effect of higher doses of this substance is accompanied with hippocampal Akt, ERK and GSK-3ß signaling alterations in adult mice.