cGMP Signaling, Phosphodiesterases and Major Depressive Disorder

Gillian Reierson, Shuyu Guo, Claudio Mastronardi, Julio Licinio, Ma-Li Wong

    Research output: Contribution to journalArticlepeer-review

    47 Citations (Scopus)


    Deficits in neuroplasticity are hypothesized to underlie the pathophysiology of major depressive disorder (MDD): the effectiveness of antidepressants is thought to be related to the normalization of disrupted synaptic transmission and neurogenesis. The cyclic adenosine monophosphate (cAMP) signaling cascade has received considerable attention for its role in neuroplasticity and MDD. However components of a closely related pathway, the cyclic guanosine monophosphate (cGMP) have been studied with much lower intensity, even though this signaling transduction cascade is also expressed in the brain and the activity of this pathway has been implicated in learning and memory processes. Cyclic GMP acts as a second messenger; it amplifies signals received at postsynaptic receptors and activates downstream effector molecules resulting in gene expression changes and neuronal responses. Phosphodiesterase (PDE) enzymes degrade cGMP into 5'GMP and therefore they are involved in the regulation of intracellular levels of cGMP. Here we review a growing body of evidence suggesting that the cGMP signaling cascade warrants further investigation for its involvement in MDD and antidepressant action.

    Original languageEnglish
    Pages (from-to)715-727
    Number of pages13
    JournalCurrent Neuropharmacology
    Issue number4
    Publication statusPublished - 2011


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