Abstract

THE WIN55, 212-2 ENIGMA IN A RESERPINE INDUCED PARKINSON MODEL

Wessam Z. Ghaith, Noha N. Nassar*, Elham A. Mobarez and Dalaal M. Abdallah

ABSTRACT

Though preclinical studies demonstrated the benefit of modulating the cannabinoid system in Parkinson disease (PD), results from clinical settings are controversial and inconclusive. Therefore, the current study addressed the effect of the synthetic cannabinoid agonist WIN55, 212-2 in a PD model induced by reserpine (Res) in rats. The post-administration of WIN55, 212-2 neither affected substantia nigral Res-induced histopathological alterations nor the reduced substantia nigral/striatal tyrosine hydroxylase (TH) immunoreactivity and striatal dopamine content induced by Res. Nevertheless, WIN55, 212-2 increased the striatal phosphorylation of mitogen-activated protein kinase p38 (MAPK p38) at both threonine 180/tyrosine 182 residues and protein kinase B (AKT) at serine 473 to consequently increase/phosphorylate nuclear factor (NF)-κB at serine 536, effects that super-passed those instigated by Res alone. Additionally, WIN55, 212-2 post-administration further increased striatal tumor necrosis factor (TNF)α and lipid peroxides versus additional depletion of the non-protein sulphydrals compared to PD rats. In light of the current results, WIN55, 212-2 post administration neither ameliorated substantia nigral histopathological alterations nor substantia nigral and/or striatal TH immunoreactivity and dopamine content, but enhanced inflammatory and oxidative stress responses-induced by the Res PD model at the molecular level.

Keywords: MAPK p38, protein kinase B, NF-?B, AKT, ROS, TH.