BDNF and major depressive disorder: It has been shown that copper blocks CREB phosphorylation, thereby reducing the expression of its downstream target protein, brain-derived neurotrophic factor (BDNF), leading to cognitive dysfunction in mice.[5] BDNF regulates cell survival, differentiation, neurite outgrowth and regeneration, and synaptic plasticity in both the central and peripheral nervous systems.[33] BDNF deficiency is strongly associated with age-related hippocampal dysfunction and may trigger memory impairment and increase the risk of depression.