Effect of Cardarine on Gene Expression of Proteins Involved in Epileptogenesis in Rat Hippocampus in the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

During the last years, the role of astro- and microglial cellsand associated neuroinflammation in the pathogenesis of epilepsyhas been extensively discussed. These cells can be in differentfunctional state. The extreme A1 and M1 phenotypes producing predominantlypro-inflammatory (promoting epileptogenesis) proteins and the A2and M2 phenotypes producing anti-inflammatory (preventing epileptogenesis)proteins. It has been suggested that the use of drugs that can stimulatepolarisation from M1 and A1 to M2 and A2 phenotypes may be a successfulstrategy for the treatment of epilepsy. Such drugs include agonistsof peroxisome proliferator-activated receptor nuclear receptors(PPARs). The aim of this study was to investigate changes in theexpression of micro- and astroglial proteins involved in the regulationof epileptogenesis in the dorsal hippocampus of rats in the lithium-pilocarpinemodel of temporal lobe epilepsy (TLE) and to investigate the effectof the PPAR agonist beta/delta cardarine on these processes. Cardarinewas administered at the initial stages of epileptogenesis (within7 days after induction of the TLE model), and two months later (chronicphase of the model) we analysed the expression of genes of interestin the dorsal hippocampus by real-time RT-PCR. The performed study revealedchanges in gene expression of astro- and microglial proteins duringepileptogenesis, mainly associated with the enhancement of neuroinflammatoryprocesses and weakening of neuroprotective properties of these cells.In TLE rats the expression of genes of markers of astro- (Gfap) and microglia activation (Aif1), pro- (Il1b, Nlrp3) and anti-inflammatory (Il1rn) proteins, markers of the A1 phenotypeof astrocytes (Lcn2, Gbp2) and growth factors (Bdnf, Fgf2)was increased. Gene expression of the protective M2 phenotype Arg1 gene was decreased in TLE rats.The most striking effect of cardarine administration was manifestedin the enhanced expression of the marker A2 gene of the S100a10 astrocyte phenotype.