The major factors involved in the age-related neurode generative disease, such as progressive decline in cognitive func tions and the loss of synaptic contacts, remain poorly under stood.There is significant evidence indicating that chronic stress and neuronal vulnerability are interrelated events contributing to age-related pathologies.An acute uncontrollable stress can im pair high-frequency stimulation-induced long-term potentiation (LTP) in the CA1 region of hippocampus, which requires the stabilization of learning-induced synaptic changes.In contrast,chronic restraint stress induces structural alterations in hipp ocampal neurons, such as a progressive decrease in the volume of hippoeampus and dendritic hypertrophy, which are correlated to behavioral deficits in hippocampal-dependent working and ref erence memory.Indeed, in response to sustained stress, the brain undergoes a complex array of cellular and molecular chan ges that lead to maladaptive remodeling and learning and memory impairment.