Metabolic gene expression changes in the hippocampus of obese epileptic male rats in the pilocarpine model of temporal lobe epilepsy.

摘要

Chronically epileptic male adult rats in the pilocarpine model of temporal lobe epilepsy (TLE), exhibited gross expansion of abdominal fat mass and significant weight gain several months after induction of status epilepticus (SE) when compared to control rats. We hypothesized that epileptogenesis can induce molecular changes in the hippocampus that may be associated with metabolism. We determined the expression levels of genes Hsd11b1, Nr3c1, Abcc8, Kcnj11, Mc4r, Npy, Lepr, Bdnf, and Drd2 that are involved in regulation of energy metabolism, in the hippocampus of age-matched control and chronic epileptic animals. Taqman-based quantitative real time polymerase chain reaction (qPCR) and the delta-delta cycle threshold (CT) methods were used for the gene expression assays. Gene expression of Hsd11b1 (cortisol generating enzyme) was significantly higher in epileptic versus control rats at 24h and 2 months, after induction of SE. Nr3c1 (glucocorticoid receptor) mRNA levels on the other hand were down-regulated at 24h, 10 days and 2 months, post SE. Abcc8 (Sur1; subunit of ATP-sensitive potassium (K(ATP)) channel) was significantly down-regulated at 10 days post SE. Kcnj11 (Kir6.2; subunit of ATP-sensitive potassium (K(ATP)) channel) was significantly up-regulated at 24h, 1 month and 2 months post SE. Thus, we demonstrated development of obesity and changes in the expression of metabolic genes in the hippocampus during epileptogenesis in male rats in the pilocarpine model of TLE.