Ethyl pyruvate prevents long-term stress-induced cognitive decline and modulates Akt/GSK-3ß signaling.

Stress is an inevitable part of life and, simultaneously, a stimulus that can trigger various neuropsychiatric disorders. Therefore, proper stress management is essential for maintaining a healthy life. In this study, we investigated the suppression of stress-induced cognitive deficit by controlling changes in synaptic plasticity caused by stress and confirmed that ethyl pyruvate (EP) has such an effect. Corticosterone, a stress hormone, suppresses long-term potentiation (LTP) in mouse acute hippocampal slices. EP blocked the LTP inhibitory effect of corticosterone by regulating GSK-3ß function. Restraint stress for 2 weeks increased the anxiety levels and caused the cognitive decline in the experimental animals. Administration of EP for 14 days did not affect the increase in anxiety caused by stress but improved cognitive decline caused by stress. In addition, the decrease in neurogenesis and synaptic function deficits in the hippocampus, which cause of cognitive decline due to stress, were improved by EP administration. These effects appear via regulation of Akt/GSK-3ß signaling, as in in vitro studies. These results suggest that EP prevents stress-induced cognitive decline through the modulation of Akt/GSK-3ß-mediated synaptic regulation.

Phyllodulcin improves hippocampal long-term potentiation in 5XFAD mice.

Alzheimer's disease (AD) is a well-known neurodegenerative brain disease, and no curative treatment has yet been developed. The main symptoms include various brain lesions, caused by amyloid ß (Aß) aggregation, and cognitive decline. Therefore, it is believed that substances that control Aß will inhibit the onset of Alzheimer's disease and slow its progression. In this study, the effect of phyllodulcin, a major component of hydrangea, on Aß aggregation and brain pathology in an animal model of AD was studied. Phyllodulcin inhibited the aggregation of Aß and decomposed the pre-aggregated Aß in a concentration-dependent manner. In addition, it inhibited the cytotoxicity of Aß aggregates. Oral administration of phyllodulcin improved Aß-induced memory impairments in normal mice, reduced Aß deposition in the hippocampus, inhibited the activation of microglia and astrocytes, and improved synaptic plasticity in 5XFAD mice. These results suggest that phyllodulcin may be a candidate for the treatment of AD.