The Effect of a Novel PDE5 Inhibitor (RF2) on Impaired Memory in Mice (RSPB 2.5)

Abstract

Neuroinflammation is a result of liberating proinflammatory mediators and thus, loss of neuronal structure and function due to the activation of resting microglia and astrocytes. The aim was to study the effect of a new phosphodiesterase-5 inhibitor, RF2 on neuroinflammation. Sildenafil was used as a positive control. Methods: The study comprised six groups of mice (n=6). LPS 0.8mg/kg i.p. was used for the induction of neuroinflammation. Morris Water Maze (MWM) and Y-maze were used for the assessment of the mice memory to determine the extent of damage/healing caused by the inflammation/treatment. Later the mice were anaesthetized, sacrificed, their brains collected and divided into hemispheres. The first was sliced and used for hematoxylin & eosin stain and nissl stain to determine the extent of damage to the brain and immunostaining for amyloid bodies and COX expression. The biochemical assays were done on the hippocampal homogenates. These assays were included IL-1β assay and MDA assay to determine the extent of damage. Results: The MWM and Y-maze showed an improvement caused by RF2 similar to that caused by sildenafil. Hematoxylin & eosin stain and nissl stain showed that the neuronal and tissue damage decreased significantly upon the application of RF2. Also, the slides showed decreased expression of amyloid proteins and increased expression of COX enzyme. IL-1β and MDA showed decreased significantly upon the administration of RF2. Conclusion: The study concluded that RF2 possess significant anti-inflammatory effects and that in can be used as an adjuvant therapy in cases of neurodegeneration.