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Changes in expression of cGMP selective phosphordiesterses 2,5 and 9 in the rat brain during aging

Nitric oxide (NO)-stimulated cGMP synthesis is present in the adult rat brain in close proximity to the NO-synthase containing structures [1]. Intracellular cGMP concentration is under very precise control and depends on parameters of its synthesis by guanylyl cyclase and degradation by phosphodiesterases (PDE). It is known that in the senescent brain the concentration of cGMP decreased [2]. When brain slices were incubated in the presence of isobutylmethylxanthine (IBMX), a nonselective phosphodiesterase inhibitor, sildenafil as a selective PDE5 inhibitor and BAY 60-7550 as a selective PDE2 inhibitor and DEANONOate as an NO donor, we have previously found that old brains are unresponsive to sildenafil treatment. Therefore in this study we wanted to investigate how the expression of cGMP selective phosphodiesterases changes in the brain during aging by using mRNA in situ hybridization.

Our results indicate differences in the expression of PDE 5 and 9 in the cerebral cortex, forebrain and caudate putamen during aging. Expression of PDE 5 is significantly decreased in old brains in comparison to adult once, which explains our previous findings with sildenafil. Expression of PDE 9 is higher in old brains comparing to adult and PDE 2 expression remains unchanged. Our findings show that cGMP metabolism is altered during brain aging.


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    de Vente J, Markerink-van Ittersum M, Axer H, Steinbusch H: Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain. Exp Brain Res. 2001, 136: 480-491. 10.1007/s002210000602.

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    Vallebuona F, Raiteri M: Age-related changes in the NMDA receptor/nitric oxide/cGMP pathway in the hippocampus and cerebellum of freely moving rats subjected to transcerebral microdialysis. Eur J Neurosci. 1995, 7: 694-701.

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This research was supported by a grant from the Internationale Stichting Alzheimer Onderzoek (02506) and by a Marie Curie Training site grant from the EC to K. Domek.

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Correspondence to Katarzyna Domek-Lopacinska.

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  • Nitric Oxide
  • Phosphodiesterase
  • PDE2 Inhibitor
  • Brain Aging
  • Phosphodiesterase Inhibitor