Mycophenolate mofetil contributes to downregulation of hippocampal interleukin type 2 and 1β mediated PI3K/AKT/mTOR pathway hyperactivation and attenuates neurobehavioral comorbidities in rat model of temporal lobe epilepsy

Publication date: Available online 20 September 2018Source: Brain, Behavior, and ImmunityAuthor(s): Arindam Ghosh Mazumder, Vikram Patial, Damanpreet SinghAbstractThe role of neuroinflammatory mediators has been well established in the pathogenesis of temporal lobe epilepsy (TLE) and associated neurobehavioral comorbidities. Mycophenolate mofetil (MMF) is commonly used as an immunosuppressant in organ transplantations and other clinical conditions. Its neuroprotective effect is well explored in different preclinical and clinical studies. The present study was designed to investigate the effect of MMF in rat model of lithium pilocarpine (LiPc)-induced spontaneous recurrent seizures and its associated neurobehavioral comorbidities. MMF treatment showed decrease in seizure severity in a dose-dependent manner, and reduced aggression in epileptic rats. There was marked improvement in spatial and recognition memory function, along with substantial decrease in depression-like behavior in MMF treated epileptic rats. There was considerable decrease in mossy fiber sprouting in the dentate gyrus and the cornu ammonis 3 regions of the hippocampus, along with reduction in neuronal death in the treated groups. Furthermore, the hippocampal mRNA level of IL-1β, IL-2, PI3K, AKT, HIF-1α, RAPTOR, mTOR, Rps6kb1 and Rps6 was found to be decreased in MMF treated animals. There was marked reduction in the protein expression of mTOR, S6, pS6, NeuN and GFAP in the rat hippocampus of the treated ani...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research