Grape-Derived Polyphenols Ameliorate Stress-Induced Depression by Regulating Synaptic Plasticity

Major depressive disorder (MDD) is associated with stress-induced immune dysregulation and reduced brain-derived neurotrophic factor (BDNF) levels in sensitive brain regions associated with depression. Elevated levels of proinflammatory cytokines and reduced BDNF levels lead to impaired synaptic plasticity mechanisms that contribute to the pathophysiology of MDD. There is accumulating evidence that the administration of polyphenols at doses ranging from 5 to 180 mg/kg of body weight can normalize elevated levels of proinflammatory cytokines and abnormal levels of BDNF and, thus, restore impaired synaptic plasticity mechanisms that mediate depressive behavior in animal models of stress. This review will focus on the mechanisms by which grape-derived polyphenols normalize impaired synaptic plasticity and reduce depressive behavior in animal models of stress.