Hesperetin rescues emotional memory and synaptic plasticity deficit in aged rats

Emotional memory deficit is often accompanied by Alzheimer's disease and normal aging. It is important to do what is possible to alleviate or rescue emotional memory deficit in aging to improve the quality of older adults. Hesperetin is a flavonoid and an aglycone of hesperidin, it easily passes through the blood-brain barrier into the brain and exerts neuroprotective effects. However, little is known about its neuroprotective effect on emotional memory in aging. To address this issue, we examined the role of hesperetin in the regulation of hippocampal long-term potentiation (LTP), surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) including glutamate receptor 1 subunit-containing AMPAR (GluA1) and glutamate receptor 1 subunit-containing AMPAR (GluA2), malondialdehyde (MDA) concentration, reduced glutathione (GSH) concentration, and associative fear memory in aged rats. We found that aged rats exhibited impaired emotional memory and LTP. Furthermore, we also found oral administration of hesperetin ameliorated the impairment of emotional memory and LTP. Finally, we demonstrated hesperetin rescued impaired LTP possibly via enhancing AMPAR trafficking and oxidant-antioxidant balance in aged rats. These results imply a pivotal role for hesperetin in synaptic plasticity and associative fear memory in aged rats and suggest that hesperetin is a potential candidate for treating emotional memory deficit in aging. (PsycInfo Database Record (c) 2021 APA, all rights reserved).