These have mainly centered on possible deficiencies in monoamines, neurotrophins, the neuroendocrine system, c-AMP, cation channels as well as neuroimmune interactions and epigenetics, however the precise mechanism or mechanisms related to depression have yet to be elucidated.
GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala.
We report here that ginkgo flavonols quercetin and kaempferol stimulates depression-related signaling pathways involving brain-derived neurotrophic factor BDNF/phosphorylation of cyclic AMP response element binding protein CREB/postsynaptic density proteins PSD95, and reduces amyloid-beta peptide (Abeta) in neurons isolated from double transgenic AD mouse (TgAPPswe/PS1e9).
Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression- and anxiety-like behaviors.
Similar studies with somatic cell mutants deficient in some component of cyclic AMP action or metabolism indicated that the depression in purine synthetic rates required G1 arrest and did not result from cell death.