Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance
Boess, F.G. ; Hendrix, M. ; Staay, F.J. van der; Erb, C. ; Schreiber, R. ; Staveren, W.C.G. ; Vente, J. de; Prikaerts, J. ; Blokland, A. ; Koenig, G. - \ 2004
Neuropharmacology 47 (2004)7. - ISSN 0028-3908 - p. 1081 - 1092.
long-term potentiation - dependent protein-kinase - soluble guanylyl cyclase - cyclic-nucleotide phosphodiesterase - messenger nitric-oxide - rat-brain - retrograde messenger - adenosine-deaminase - serotonin receptor - nmda receptors
An essential element of the signalling cascade leading to synaptic plasticity is the intracellular second messenger molecule guanosine 3¿,5¿-cyclic monophosphate (cGMP). Using the novel, potent, and selective inhibitor Bay 60-7550, we show that the enzyme 3¿,5¿-cyclic nucleotide phosphodiesterase type 2 (PDE2) is responsible for the degradation of newly synthesized cGMP in cultured neurons and hippocampal slices. Inhibition of PDE2 enhanced long-term potentiation of synaptic transmission without altering basal synaptic transmission. Inhibition of PDE2 also improved the performance of rats in social and object recognition memory tasks, and reversed MK801-induced deficits in spontaneous alternation in mice in a T-maze. Our data provide strong evidence that inhibition of PDE2 can improve memory functions by enhancing neuronal plasticity