Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec;9(4):715-27.
doi: 10.2174/157015911798376271.

cGMP Signaling, Phosphodiesterases and Major Depressive Disorder

Gillian W Reierson  1 , Shuyu Guo, Claudio Mastronardi, Julio Licinio, Ma-Li Wong
Affiliations

cGMP Signaling, Phosphodiesterases and Major Depressive Disorder

Gillian W Reierson et al. Curr Neuropharmacol. 2011 Dec.

Abstract

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.

Keywords: Major Depression; antidepressants; cyclases; cyclic guanosine monophosphate; neurogenesis; neuroplasticity; pharmacology.; phophodiesterases.

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
The cGMP signaling pathway. Presynaptic (top) and postsynaptic (bottom) elements of the cGMP signaling cascade are represented. AMPAR = 2-amino-3-(5-methyl-3-oxo-1,2-oxal-4-yl)propanoic acid receptor; CaMK = calcium-calmodium-dependent kinase; cAMP = cyclic adenosine monophosphate; cGMP = cyclic guanosine monophosphate; CNG = cyclic nucleotide gated channels; NO = nitric oxide; nNO = neuronal NO; PDE = phosphodiesterase; PI3K/AKT/Gsk3 = phosphoinositide 3-kinase/protein kinase B (aka AKT)/glycogen synthase kinase 3; PKGI = cGMP dependent protein kinase I; PKGII = cGMP dependent protein kinase II; sGC = soluble guanylate cyclase; VASP = vasodilator-stimulated phosphoprotein.
See this image and copyright information in PMC

References

    1. Blazer DG, Kessler RC, Swartz MS. Epidemiology of recurrent major and minor depression with a seasonal pattern. The National comorbidity survey. Br. J. Psychiatry. 1998;172:164–167. - PubMed
    1. Wong ML, Licinio J. From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat. Rev. Drug. 2004;Discov. 3:136–151. - PubMed
    1. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol. Psychiatry. 2006;59:1116–1127. - PubMed
    1. Duman CH, Schlesinger L, Russell DS, Duman RS. Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Res. 2008;1199:148–158. - PMC - PubMed
    1. Chen CC, Yang CH, Huang CC, Hsu KS. Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity. Neuropsychopharmacology. 2010;35:1605–1617. - PMC - PubMed